Loratadine

Selective Peripheral Histamine H1 Receptor Binding and Inverse Agonism

This compound demonstrates selective binding to peripheral histamine H1 receptors. wikipedia.orgdrpress.orgdrugbank.com Unlike some older antihistamines, this selectivity contributes to its non-sedating profile. wikipedia.orgdrpress.orgdrugbank.comwikipedia.org this compound functions as an inverse agonist at the H1 receptor. drugbank.comresearchgate.netnih.govlymphosign.com

Histamine H1 receptors belong to the superfamily of G-protein coupled receptors (GPCRs). nih.govdrugbank.comlymphosign.comnih.gov These receptors exist in a dynamic equilibrium between active and inactive conformations. drugbank.com Histamine binding stabilizes the active form of the H1 receptor, promoting its interaction with Gq/11 proteins and subsequent intracellular signaling cascades. researchgate.netlymphosign.com

As an inverse agonist, this compound binds to the H1 receptor at a site distinct from histamine, favoring and stabilizing the inactive conformation of the receptor. drugbank.comresearchgate.netnih.govlymphosign.com This action shifts the equilibrium towards the inactive state, thereby reducing the constitutive activity of the H1 receptor and preventing or reducing histamine-mediated symptoms. drugbank.comresearchgate.netnih.govlymphosign.com

Interaction with G-Protein Coupled Receptors

Lack of Significant Central Nervous System (CNS) H1 Receptor Affinity

A key characteristic of this compound is its poor penetration into the central nervous system and low affinity for CNS H1 receptors. wikipedia.orgdrpress.orgdrugbank.comhres.ca This property is primarily attributed to its lower lipid solubility compared to first-generation antihistamines and its interaction with P-glycoprotein, which is involved in clearing certain drugs from the CNS. drpress.orgdrugbank.com The limited CNS penetration is responsible for the reduced incidence of sedative and cognitive side effects commonly associated with older antihistamines. wikipedia.orgdrpress.orgdrugbank.comnih.govclevelandclinic.org

Modulation of Histamine-Mediated Cellular Responses

By selectively blocking peripheral H1 receptors, this compound modulates various cellular responses triggered by histamine. This includes reducing vascular permeability, which helps prevent edema and flushing, and decreasing smooth muscle tone, contributing to bronchodilation. bocsci.comnih.gov this compound also affects peripheral nociceptive receptors, minimizing pain and itching. bocsci.comnih.gov At higher concentrations, second-generation antihistamines like this compound can inhibit the release of histamine from mast cells and basophils. bocsci.comnih.gov This can lead to reduced expression of intercellular adhesion molecule-1 (ICAM-1) in epithelial cells, thereby inhibiting type 1 hypersensitivity reactions. bocsci.comnih.gov

Anti-Inflammatory Properties and Associated Mechanisms

This compound, traditionally recognized as an antihistamine, has demonstrated anti-inflammatory activities through various molecular and cellular mechanisms, often independent of its histamine H1-receptor antagonism wikipedia.orgmdpi.com. These properties contribute to its therapeutic effects beyond simply blocking histamine.

Inhibition of Mediator Release from Mast Cells and Basophils

This compound and its primary metabolite, descarboethoxythis compound (des-loratadine), have been shown to inhibit the release of various inflammatory mediators from human mast cells and basophils researchgate.netnih.gov. Studies have demonstrated that this compound at micromolar concentrations can prevent the release of histamine and leukotriene C4 from activated rat peritoneal mast cells and cloned murine mast cell lines bocsci.com. Similarly, both this compound and des-loratadine exhibit concentration-dependent inhibition of histamine, tryptase, leukotriene C4 (LTC4), and prostaglandin D2 (PGD2) release from purified human basophils and mast cells challenged with allergens or anti-FcεRI antibodies researchgate.netnih.gov. The inhibitory effect on histamine release from human basophils by descarboethoxythis compound has been observed at doses above 2 µM, while this compound showed this effect at doses above 7 µM in different experimental systems capes.gov.br. This inhibition of mediator release is suggested to involve the impairment of intracellular calcium increase following cell activation capes.gov.br.

Here is a summary of mediator release inhibition by this compound and Des-loratadine:

Modulation of ICAM-1 Expression in Epithelial Cells

This compound has been shown to decrease the expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of epithelial cells researchgate.net. ICAM-1 plays a crucial role in the recruitment of inflammatory cells to the site of inflammation. Studies using cultured primary bronchial or transformed respiratory epithelial cells have demonstrated that both this compound and desthis compound can inhibit rhinovirus-induced ICAM-1 upregulation in a dose-dependent manner researchgate.net. They also inhibited ICAM-1 mRNA induction and completely blocked rhinovirus-induced ICAM-1 promoter activation researchgate.net. In patients with pollen allergy, this compound treatment reduced ICAM-1 expression on nasal epithelial cells nih.govhunimed.eu. Furthermore, this compound and descarboethoxythis compound significantly blocked the increase in ICAM-1 expression on nasal epithelial cells activated by histamine nih.gov. This modulation of ICAM-1 expression by this compound suggests a mechanism for reducing inflammatory cell infiltration.

Suppression of NF-κB Pathway Signaling

A key mechanism by which this compound exerts its anti-inflammatory effects is through the suppression of the NF-κB signaling pathway wikipedia.orgresearchgate.netnih.gov. The NF-κB pathway is a critical regulator of inflammatory responses, controlling the transcription of numerous pro-inflammatory genes. This compound has been shown to specifically inhibit the NF-κB pathway researchgate.netnih.gov.

Suppression of the NF-κB pathway by this compound leads to a reduction in the levels of various pro-inflammatory cytokines researchgate.netnih.goviiarjournals.org. In LPS-treated macrophages, this compound treatment reduced the levels of nitric oxide, inducible nitric oxide synthase (iNOS), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) researchgate.netnih.gov. The reduction in IL-6 and TNF-α levels is a direct consequence of the inhibited NF-κB signaling, as these cytokines are regulated by this pathway researchgate.netnih.goviiarjournals.org. This suppression of pro-inflammatory cytokine production is a significant aspect of this compound's anti-inflammatory profile.

Here is a table summarizing the effect of this compound on Pro-inflammatory Cytokines:

Targeting Syk and Src Proteins

Investigation of AP-1 Signaling Pathway Modulation

Beyond the NF-κB pathway, studies have also investigated the modulation of the Activator Protein 1 (AP-1) signaling pathway by this compound researchgate.netresearchgate.netnih.gov. The AP-1 pathway is another crucial transcription factor involved in regulating inflammatory gene expression. Research indicates that this compound can suppress the AP-1 signaling pathway researchgate.netresearchgate.netnih.gov. This suppression is suggested to occur through the inhibition of TAK1 (transforming growth factor-β-activated kinase 1), an upstream kinase in the AP-1 pathway researchgate.netresearchgate.netnih.gov. By inhibiting TAK1 activation, this compound suppresses the downstream components of the AP-1 pathway, including the expression of AP-1 subunits like c-Jun and c-Fos, and the phosphorylation of kinases such as JNK, MKK7, and TAK1 itself mdpi.comresearchgate.netnih.gov. This leads to a reduction in the transcription of inflammation-related enzymes, including matrix metalloproteinases (MMPs) researchgate.netnih.gov. The modulation of the AP-1 pathway by targeting TAK1 represents an additional mechanism contributing to this compound's anti-inflammatory effects researchgate.netresearchgate.netnih.gov.

Mild Anticholinergic Activity Research

Studies have investigated the potential for this compound to exhibit anticholinergic activity. While second-generation antihistamines are generally associated with a lower incidence of anticholinergic effects compared to their first-generation counterparts, research indicates that this compound may possess mild activity in this regard.

In vitro studies using functional bioassays, such as measuring the inhibition of carbachol-induced contractions in isolated guinea pig trachealis muscle, have shown this compound to have anticholinergic potency. nih.gov The rank order of anticholinergic potencies among several antihistamines in one in vitro study placed this compound after cyproheptadine, promethazine, desthis compound, and diphenhydramine. nih.gov

In vivo studies in animal models, including mice, rats, and monkeys, have also assessed this compound's anticholinergic effects by observing metrics such as mydriasis (pupil dilation) and reduced fecal excretion. hres.ca While some anticholinergic effects were observed in long-term studies in rats and monkeys at higher doses, this compound did not exhibit in vivo anticholinergic activity as measured by the lack of mydriasis in mice or rats at oral doses up to 200 mg/kg, in dogs up to 60 mg/kg, and in monkeys up to 90 mg/kg. hres.ca Furthermore, this compound did not antagonize physostigmine-induced lethality, another measure of anticholinergic activity, at oral doses up to 320 mg/kg in mice. hres.ca

Despite these findings, the anticholinergic activity of this compound is considered mild, contributing to its favorable safety profile regarding central nervous system (CNS) effects compared to first-generation antihistamines. optoceutics.com

Interaction with Voltage-Gated Inwardly Rectifying Potassium Channel KCNH2 (hERG)

The human ether-a-go-go-related gene (hERG), which encodes the voltage-gated potassium channel KCNH2, is critical for cardiac repolarization. genecards.orgdrugbank.com Blockade of the hERG channel can lead to QT interval prolongation and increase the risk of potentially fatal arrhythmias, such as torsade de pointes. Research has examined the interaction of this compound with the hERG channel.

Studies using stably transfected HEK cells expressing the hERG channel have demonstrated that this compound can block this channel. researchgate.netnih.gov One study reported a mean IC₅₀ value of 173 nM for this compound's blockade of hERG current amplitude at a pacing rate of 0.1 Hz. researchgate.net Another in vitro study using automated patch-clamp reported an observed IC₅₀ value of 5.15 µM for this compound. nih.gov

It is important to note that while this compound has shown the ability to block the hERG channel in vitro, its clinical cardiac profile is considered safer compared to some other antihistamines like terfenadine, despite similar potency in some in vitro hERG block assays. researchgate.net The reasons for this difference may be related to how the drugs block the channel or other factors. researchgate.net

Inhibition of Amino Acid Transporters (e.g., B⁰AT2)

Recent research has identified that this compound can act as an inhibitor of certain amino acid transporters, particularly the neutral amino acid transporter B⁰AT2 (SLC6A15). researchgate.netacs.orgacs.org B⁰AT2 is a sodium-dependent membrane transporter belonging to the SLC6 family, expressed predominantly in the brain, and involved in the uptake of neutral amino acids. researchgate.netnih.gov It has been implicated in mood and metabolic disorders. researchgate.netnih.gov

A screening of a library of bioactive compounds identified this compound as a selective inhibitor of B⁰AT2. researchgate.netacs.orgacs.org In concentration-dependent assays, this compound inhibited the uptake of [³H]proline by B⁰AT2 with an IC₅₀ value of 4 µM in HEK293 cells overexpressing B⁰AT2. acs.org This inhibition was confirmed to be reversible through electrophysiology experiments. acs.orgacs.org

This compound has shown selectivity for B⁰AT2 within the SLC6 family, exhibiting significantly weaker activity against transporters for GABA (GAT1, GAT2-4) and being inactive against transporters for serotonin (SERT), dopamine (DAT), and its closest homologue NTT4/SLC6A17. acs.org

Understanding the molecular basis of this compound's inhibition of B⁰AT2 has also led to the discovery of other potential inhibitors of this transporter. nih.gov

IC₅₀ Values for this compound Inhibition of B⁰AT2

This research highlights a pharmacological action of this compound beyond its well-established antihistaminergic effects, suggesting potential interactions with amino acid transport systems.

Rapid Oral Absorption Characteristics

This compound is rapidly and well-absorbed from the gastrointestinal tract following oral administration. medicines.org.ukmedcentral.compatsnap.comdrugs.commedsafe.govt.nz Peak plasma concentrations of this compound are typically achieved relatively quickly, generally between 1 to 1.5 hours after administration of conventional tablets. medicines.org.ukmedcentral.commedsafe.govt.nz Some sources indicate peak concentrations can occur between 1 and 2 hours, or even up to 3.7 hours depending on the formulation and study. medcentral.comdrugs.comdrugbank.com The rapid absorption contributes to the relatively fast onset of antihistaminic action, which is often observed within 1-4 hours. medcentral.com

Impact of First-Pass Hepatic Metabolism on Bioavailability

Despite being well-absorbed, this compound undergoes extensive first-pass metabolism in the liver. medicines.org.ukpatsnap.comdrugs.commedsafe.govt.nzdrugbank.comwikipedia.orgresearchgate.nettandfonline.com This significant metabolic transformation upon initial passage through the liver substantially impacts its oral bioavailability. tandfonline.comtandfonline.comnih.gov The primary enzymes responsible for this metabolism are cytochrome P450 (CYP) isoenzymes, mainly CYP3A4 and CYP2D6. medicines.org.ukpatsnap.comdrugs.commedsafe.govt.nzdrugbank.comwikipedia.orgresearchgate.netmims.com This metabolic process converts this compound into its major active metabolite, desthis compound (also known as descarboethoxythis compound). medicines.org.ukpatsnap.comdrugs.commedsafe.govt.nzdrugbank.comwikipedia.org Desthis compound is pharmacologically active and is responsible for a significant portion of the clinical effect of this compound. medicines.org.ukmedsafe.govt.nzdrugbank.com The extensive first-pass metabolism results in a lower systemic exposure to the parent drug (this compound) compared to its active metabolite desthis compound. fda.gov

Food intake can slightly delay the absorption of this compound, but generally without affecting the clinical effect. medicines.org.ukmedsafe.govt.nz However, some studies suggest food may increase the extent of this compound absorption and potentially increase peak plasma concentrations and AUCs, while delaying the time to peak plasma concentration for both this compound and its metabolite. medcentral.commims.com The bioavailability parameters of this compound and its active metabolite are generally dose proportional. medicines.org.ukmedsafe.govt.nz

Inter-individual Variability in Absorption

This compound oral absorption can exhibit a high degree of inter-subject variability. tandfonline.comtandfonline.comnih.gov This variability is likely influenced by factors such as differences in the activity of the metabolizing enzymes, particularly the polymorphic CYP2D6, CYP2C19, and CYP3A4 enzymes. researchgate.net Studies have noted large coefficients of variation for pharmacokinetic parameters like Cmax and AUC for this compound, reflecting this variability. fda.govhres.cahres.ca For example, in pediatric subjects aged 2-5 years, the intersubject variability (expressed as coefficient of variation) for Cmax and AUC for this compound was reported as 90% and 80%, respectively. fda.gov

Research exploring alternative delivery methods, such as buccal administration, has shown potential in reducing the inter-individual variability in this compound absorption. tandfonline.comtandfonline.comnih.govresearchgate.net

Plasma Protein Binding Characteristics (97-99%)

This compound is highly bound to plasma proteins in humans, with reported binding ranging from 97% to 99%. medicines.org.ukdrugs.commedsafe.govt.nzdrugbank.comwikipedia.orghres.canih.govhres.cafda.gov Its major active metabolite, desthis compound, is also bound to plasma proteins, though to a lesser extent, typically between 73% and 77%. medicines.org.ukdrugs.commedsafe.govt.nzwikipedia.orghres.cahres.cafda.gov This high degree of protein binding for the parent compound means that only a small fraction of the circulating this compound is unbound and available to exert pharmacological effects or be metabolized and excreted.

Volume of Distribution Investigations (120 L/Kg)

This compound has a large apparent volume of distribution, reported as approximately 120 L/kg. drugbank.comnih.govfda.govpharmacompass.com This large volume of distribution suggests that this compound is extensively distributed into body tissues outside of the plasma. medcentral.comresearchgate.net While the distribution into specific human body tissues and fluids has not been fully determined, studies in animals indicate wide distribution, with the lowest concentrations observed in the brain, which aligns with its classification as a non-sedating antihistamine due to limited blood-brain barrier penetration. medcentral.comhres.cafda.gov Large clearance values observed after oral administration also support the notion of extensive presystemic metabolism and/or tissue distribution in humans. medcentral.com

Here is a summary of some pharmacokinetic parameters:

Note: Values may vary slightly depending on the specific study and formulation used.

Central Nervous System Penetration Analysis and P-glycoprotein Involvement

This compound is characterized by poor penetration into the central nervous system. drugbank.comwikipedia.org This limited CNS entry is a significant factor in its classification as a non-sedating antihistamine, as it results in a lack of CNS depressant effects such as drowsiness and impaired psychomotor function. drugbank.com

Studies have indicated that P-glycoprotein (P-gp), an efflux pump located at the blood-brain barrier, plays a role in limiting the brain penetration of second-generation antihistamines, including this compound. drugbank.comnih.govnih.gov Research using in situ brain perfusion techniques in rats has shown that while this compound achieved substantial brain penetration, this penetration was further increased when P-gp was inhibited. nih.gov Similarly, studies using multidrug-resistant (mdr) gene 1a and 1b knockout mice demonstrated that the brain-to-plasma area under the curve (AUC) ratio for this compound was higher in knockout mice lacking functional P-gp compared to wild-type mice, indicating that P-gp limits this compound's entry into the brain. nih.gov This suggests that P-gp actively transports this compound out of the CNS. drugbank.comnih.gov

Tissue Distribution Studies in Preclinical Models

Preclinical studies in animals, including rats and monkeys, using radiolabeled this compound have provided insights into its tissue distribution. These studies have shown that this compound and its metabolites are widely distributed throughout the tissues examined. nih.govnih.govresearchgate.nethres.ca

In rats, concentrations of radioactivity were found to be highest in the lungs, liver, kidneys, adrenal glands, pituitary gland, and spleen. nih.govresearchgate.nethres.ca The lowest concentrations were observed in the brain, supporting the findings of limited CNS penetration. nih.govhres.ca Radioactivity in all tissues was observed to decrease over time, with no evidence of drug accumulation in tissues with multiple dosing. hres.ca

A study in rats specifically investigating the tissue distribution of this compound, desthis compound, and their hydroxylated metabolites (6-OH-DL, 5-OH-DL, and 3-OH-DL) found that these compounds were widely distributed in the liver, spleen, thymus, heart, adrenal glands, and pituitary gland. nih.govresearchgate.netebi.ac.uk In immune-regulatory tissues, the concentrations of this compound, desthis compound, and their active metabolites were significantly higher in the spleen compared to the thymus. nih.govresearchgate.netebi.ac.uk this compound concentration in the heart was highest after the liver and adrenal glands, while the concentrations of desthis compound and its hydroxylated metabolites were generally higher in the liver, adrenal glands, and spleen than in the heart. nih.govresearchgate.netebi.ac.uk

Formation of Descarboethoxythis compound (Desthis compound)

Pharmacological Activity of Desthis compound (4 times more active)

Desthis compound is significantly more potent than this compound itself as an H1 receptor antagonist. nih.gov Preclinical studies have indicated that the affinity of desthis compound for the H1 receptor is substantially higher, reported to be between 50 and 194 times greater than that of this compound. medicopublication.com This increased affinity contributes to desthis compound being described as approximately 4 times more pharmacologically active than this compound. drugbank.com

Subsequent Metabolism of Desthis compound

Desthis compound undergoes further metabolism in the body. europa.euwikipedia.org The formation of its major human metabolite, 3-hydroxydesthis compound, involves a sequential process. nih.govresearchgate.netbioivt.com

The initial step in the dominant metabolic route of desthis compound involves N-glucuronidation. europa.euwikipedia.orghelsinki.fihelsinki.fi This reaction is catalyzed by UDP-Glucuronosyltransferase 2B10 (UGT2B10). europa.eunih.govresearchgate.netbioivt.comresearchgate.net This glucuronidation by UGT2B10 is considered an obligatory requirement for the subsequent formation of 3-hydroxydesthis compound. europa.eubioivt.com

Following N-glucuronidation by UGT2B10, the desthis compound N-glucuronide undergoes 3-hydroxylation. europa.euwikipedia.orgresearchgate.nethelsinki.fi This hydroxylation step is catalyzed by the cytochrome P450 enzyme CYP2C8, leading to the formation of 3-hydroxydesthis compound. europa.eunih.govresearchgate.netbioivt.comhelsinki.firesearchgate.net This metabolic pathway highlights a central role for CYP2C8 in the biotransformation of desthis compound to its major hydroxylated metabolite in humans. helsinki.firesearchgate.net The process is completed by a subsequent rapid, non-enzymatic deconjugation of the N-glucuronide. wikipedia.orgnih.govresearchgate.net

Glucuronidation by UGT2B10

Other Hydroxylated Metabolites (e.g., 6-hydroxy desthis compound, 5-hydroxy desthis compound)

In addition to 3-hydroxydesthis compound, other hydroxylated metabolites of desthis compound exist. thieme-connect.com These include 6-hydroxy desthis compound and 5-hydroxy desthis compound. thieme-connect.com Research indicates that these metabolites, along with 3-hydroxy desthis compound, are considered active due to their ability to inhibit the binding of pyrilamine to rat brain H1 receptors. thieme-connect.com While 3-hydroxylation is the primary route in humans, animal studies have shown different metabolic profiles with more 5- and 6-hydroxylation compared to 3-hydroxylation observed in humans. europa.eu 5-hydroxy desthis compound is formed via hepatic cytochrome P450-mediated oxidation of desthis compound and is considered a major hydroxylated metabolite contributing to antihistaminic activity.

Renal and Fecal Excretion Proportions

Studies in humans show that approximately 40% of the administered dose of this compound is excreted in the urine over a 10-day period. wikipedia.orgdrugbank.comhres.cahres.canih.govmedsafe.govt.nzdafrapharma.com A similar proportion, approximately 42% of the dose, is eliminated in the feces over the same 10-day period. wikipedia.orgdrugbank.comhres.cahres.canih.govmedsafe.govt.nzdafrapharma.com This excretion is primarily in the form of conjugated metabolites. medsafe.govt.nzdafrapharma.com Less than 1% of the active substance is excreted unchanged as either this compound or desthis compound. medsafe.govt.nzdafrapharma.com Approximately 27% of the dose is eliminated in the urine within the first 24 hours. hres.cahres.camedsafe.govt.nzdafrapharma.com

Here is a summary of the excretion profile:

Clearance Rates

The clearance of this compound has been reported after single oral doses. Following a 20 mg single oral dose, the clearance rate of this compound is approximately 12 L/h/kg. nih.govdrugbank.com After a 40 mg single oral dose, the clearance rate is approximately 9 L/h/kg. nih.govdrugbank.com P-glycoprotein is involved in the clearance of second-generation antihistamines, including this compound, from the central nervous system. nih.govdrugbank.com Patients with hepatic impairment or renal insufficiency (glomerular filtration rate less than 30 mL/minute), including geriatric patients, have decreased clearance of the drug. medcentral.comdrugs.com

Pharmacokinetics in Specific Patient Populations (e.g., pediatric, geriatric, renally impaired)

Pharmacokinetic studies have investigated the disposition of this compound in various patient populations.

Renally Impaired Patients: In adults with chronic renal impairment (creatinine clearance of 30 mL/minute or less), both the oral bioavailability and peak plasma concentrations (Cmax) of this compound and desthis compound may be increased compared to individuals with normal renal function. nafdac.gov.ngmedcentral.com Specifically, peak plasma concentrations and AUCs of this compound were increased by about 73%, and those of desthis compound were increased by about 120% in adults with impaired renal function compared to those with normal renal function. medcentral.com However, as mentioned earlier, the elimination half-lives of this compound and its active metabolite appear to be similar to those in individuals with normal renal function. nafdac.gov.ngmedcentral.comdrugs.commedicines.org.uk Hemodialysis does not appear to significantly affect the pharmacokinetics of this compound or desthis compound. nafdac.gov.ngmedcentral.commedicines.org.uk

Geriatric Patients: In geriatric adults (66-78 years of age), peak plasma concentrations and AUCs of this compound and its metabolite were increased by 50% compared to younger adults. medcentral.com Geriatric patients frequently have decreased renal function, which can contribute to decreased clearance of the drug. medcentral.comdrugs.com

Pediatric Patients: Recommended pediatric doses are based on comparisons of this compound pharmacokinetics in adults and children. medcentral.com Safety profiles from studies in adults and children at recommended or higher doses were also considered. medcentral.com For children 2 to 5 years of age with renal insufficiency, a lower initial dose is recommended. nafdac.gov.ng Similarly, for children 6 years of age and older with renal insufficiency (GFR < 30 mL/min), a lower initial dose is advised. nafdac.gov.ngdrugs.com

Dose Proportionality Research

Studies have investigated the dose proportionality of this compound and its active metabolite. Following single oral doses of 10, 20, or 40 mg of this compound, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of both this compound and its active metabolite, desthis compound, are proportional to the administered dose. nih.govmedcentral.com This indicates linear pharmacokinetics over this dose range. For this compound, Cmax values of 4.7, 10.8, and 26.1 ng/mL were observed at 1.5, 1.0, and 1.2 hours after 10, 20, and 40 mg doses, respectively. nih.govhres.ca For descarboethoxythis compound, Cmax values of 4.0, 9.9, and 16.0 ng/mL were reached at 3.7, 1.5, and 2.0 hours after the same doses. nih.govhres.ca The AUC- and Cmax-dose relationships were linear, and there were no significant differences in half-life or dose-adjusted AUC values among the different dose treatments. nih.gov

Steady-State Plasma Concentrations

Following once-daily administration of this compound, steady-state plasma concentrations of both this compound and its active metabolite, desthis compound, are typically achieved by the fifth day of administration. hres.cahres.cahres.canih.govmedcentral.com At steady state, there is little accumulation of the unchanged drug. nih.govmedcentral.com In one study where healthy male volunteers received 40 mg of this compound daily for 10 days, steady-state plasma this compound Cmax concentrations were reached at 1.5 hours after each dose. nih.gov Descarboethoxythis compound steady-state Cmax values ranged from 26 to 29 ng/mL, with Tmax ranging from 1.8 to 3 hours. nih.gov The AUC at steady state (AUCτ) was 80 to 96 hng/mL for this compound and 349 to 421 hng/mL for descarboethoxythis compound. nih.gov The AUC of this compound is less than that of desthis compound at steady state; in one study, the AUC of the drug was about 23% of that of its metabolite at steady-state concentrations occurring from the fifth to the tenth day of administration. medcentral.com Reported clinical results suggest that the steady state mean (%CV) plasma Cmax and AUC(24hr) of this compound were 4.73 ng/ml (119%) and 24.1 ng.hr/ml (157%), respectively, after dosing with 10 mg this compound tablets for 10 days. researchgate.net High inter-subject variability in this compound steady-state data is likely due to the characteristics of the CYP2D6, CYP2C19, and CYP3A4 enzymes involved in its metabolism. researchgate.net

Here is a table showing steady-state pharmacokinetic parameters for this compound and descarboethoxythis compound after 10 mg daily dosing for 10 days:

Starting Materials and Intermediate Compounds

Classical synthesis routes for this compound typically utilize intermediates containing pyridine rings as starting materials. One common starting material is 2-cyano-3-methylpyridine. drpress.org Another route may begin with a tricyclic ketone, specifically 8-chloro-5,6-dihydro-11H-benzo patsnap.comcyclohepta[1,2-b]pyridin-11-one.

Key intermediates in this compound synthesis include those formed during reactions such as the Ritter reaction and subsequent transformations. For instance, the Ritter reaction involving 2-cyano-3-methylpyridine and tert-butanol in sulfuric acid yields an intermediate amide product. researchgate.net Another important intermediate is 8-chloro-5,6-dihydro-11H-benzo patsnap.comcycloheptyl[1,2-b]pyridin-11-one, which can be obtained through cyclization reactions. patsnap.com

Key Reaction Steps and Methodologies

The synthesis of this compound involves several key reaction steps, including the Ritter reaction, alkylation, cyclization, and the Wittig reaction. drpress.orgdrpress.org

The Ritter reaction is a significant step in some this compound synthesis routes, particularly those starting from 2-cyano-3-methylpyridine. This reaction involves the addition of a nitrile to a carbocation, typically generated from an alcohol or alkene in the presence of a strong acid, to form an intermediate nitrilium ion, which is then hydrolyzed to an amide. researchgate.net

The Wittig reaction is another methodology employed in this compound synthesis. This reaction involves the reaction of an aldehyde or ketone with a phosphorus ylide to form an alkene. scribd.com In one classical route, a Wittig reaction is used to construct the final alkene moiety of this compound. This route may involve the reduction of a tricyclic ketone, followed by chlorination and reaction with an organophosphorus reagent, culminating in a Wittig reaction to synthesize this compound. drpress.org Another classical route utilizing 2-cyano-3-methylpyridine also incorporates a Wittig cyclization step. drpress.org While the Wittig reaction can be effective, it may involve complex steps and require precise control of reaction conditions, sometimes making it more suitable for laboratory research than large-scale industrial production. drpress.org Challenges such as by-product formation can also complicate industrial implementation. drpress.org

Ritter Reaction and its Optimization

Optimization of Reaction Conditions, Yields, and Environmental Impact

Optimization efforts in this compound synthesis aim to improve reaction conditions to enhance yields, reduce production costs, and minimize environmental impact. drpress.orgdrpress.org Classical routes, while widely used in laboratory research, can present challenges in controlling reaction conditions and product purification, particularly in large-scale production, where by-products can affect quality. drpress.org

Improved synthesis methods have focused on enhancing efficiency and reducing environmental impact. drpress.orgdrpress.org This includes optimizing reaction conditions for the Ritter reaction to improve selectivity and reduce energy consumption and by-product formation. drpress.org Alkylation reactions have also been improved through the introduction of new reagents to increase selectivity and yield while reducing environmental pollution. drpress.orgdrpress.org Optimization of cyclization reactions, which form the tricyclic structure of this compound, has involved using novel catalysts to reduce side reactions and increase yields. drpress.org These improvements contribute to a more efficient, environmentally friendly, and cost-effective synthesis suitable for large-scale production. drpress.org

Introduction of Novel Catalysts

The introduction of novel catalysts has played a significant role in the progress of this compound synthesis. drpress.orgdrpress.org Novel catalysts and optimized reaction conditions have led to significant advancements in recent years. drpress.orgdrpress.org In improved cyclization reactions, novel catalysts are utilized to reduce side reactions and enhance yields in the formation of this compound's tricyclic structure. drpress.org For example, one improved method substitutes high-cost, strong acid catalysts like trifluoromethanesulfonic acid with a boric acid–sulfuric acid system in the cyclization step, reducing corrosion risks and catalyst costs. Palladium catalysts have also been explored for intramolecular cyclization reactions in the synthesis of this compound intermediates. google.com The use of novel catalysts contributes to making this compound synthesis more efficient and environmentally friendly. drpress.org

Design and Synthesis of Analogues for SAR Elucidation

The design and synthesis of this compound analogues for SAR studies involve systematic modifications to the core structure. Researchers have introduced various substituents and functional groups to different parts of the molecule to explore their impact on activity. For instance, the introduction of hydroxyl groups and chiral centers into this compound derivatives has been explored to enhance affinity for H1 receptors rsc.orgrsc.org. Synthetic routes often involve key steps such as Michael addition, Dieckmann cyclization, and coupling reactions rsc.orgrsc.org. Late-stage lead diversification approaches, coupled with techniques like quantitative NMR spectroscopy, have enabled the synthesis and characterization of numerous analogues (on a nanomole scale) to identify new SAR vectors acs.orgnih.gov.

Impact of Structural Modifications on H1 Receptor Affinity and Selectivity

Structural modifications to the this compound scaffold have a significant impact on H1 receptor affinity and selectivity. The removal of the ethoxycarbonyl group attached to the piperidine ring in this compound results in its active metabolite, desthis compound. This modification leads to a substantially higher affinity for the H1 receptor compared to the parent compound nih.govnih.gov. Studies have shown that desthis compound binds with approximately 100-fold higher affinity to the H1 receptor than this compound researchgate.net. The tricyclic group of desthis compound is deeply embedded in the orthosteric pocket of the H1 receptor, interacting with hydrophobic residues, while the piperidine ring forms an electrostatic interaction with aspartate residue D1073.32 nih.gov. Substitutions on the pyridine ring (A ring) of this compound can also affect activity; for example, substituents in the 2- and 4-positions generally reduced activity, although some modifications at the 3-position were tolerated acs.org.

Exploration of Activity against Other Biological Targets (e.g., B0AT2)

Beyond their primary activity as H1 receptor antagonists, this compound and its analogues have been explored for activity against other biological targets. Notably, this compound has been identified as a selective inhibitor of the amino acid transporter B0AT2 (SLC6A15) researchgate.netacs.orgfigshare.com. B0AT2 is primarily expressed in the brain and has been implicated in mood and metabolic disorders researchgate.netacs.orgacs.orgfigshare.com. This compound inhibits proline uptake by B0AT2 with an IC50 value of 4 µM, demonstrating selectivity over several other members of the SLC6 family acs.orgacs.org. However, the SAR for B0AT2 inhibition appears to diverge from the SAR for H1 receptor activity researchgate.net. For instance, while desthis compound has higher affinity for the H1 receptor, it is only a weak inhibitor of B0AT2 researchgate.net. This compound analogues have also been described as inhibitors of other targets, including 5-lipoxygenase, platelet-activating factor (PAF), farnesyl protein transferase (FPT), and K2p18.1 channels, although the SAR for these targets differs from that for B0AT2 researchgate.net.

Influence of N-oxidation on Antihistamine Activity and Enantiomeric Stability

N-oxidation of this compound and related analogues has been shown to affect antihistamine activity in an enantiomer-dependent fashion and can lead to stable, helically chiral products nih.govacs.orgnih.gov. Studies involving N-oxidized analogues of this compound and desthis compound have revealed that rigidifying the core structure through N-oxidation impacts their activity nih.gov. For example, in one study, while both enantiomers of an N-oxidized this compound analogue were relatively inactive, the (−)-enantiomer showed greater activity than the (+)-enantiomer nih.gov. This contrast was more pronounced with an N-oxidized desthis compound analogue, where the (−)-enantiomer exhibited significant antagonist activity compared to the (+)-enantiomer nih.gov. These findings suggest that conformational dynamics and the resulting helical chirality play a role in the biological activity of these compounds nih.gov.

Computational Docking Studies in SAR Analysis

Computational docking studies are valuable tools in SAR analysis, providing insights into the potential binding interactions between ligands and their target proteins researchgate.netnih.govnih.gov. For this compound and its analogues, docking studies have been used to illustrate observed differences in antihistamine activity, particularly in the context of N-oxidation and enantiomer-dependent activity nih.gov. Molecular docking can help predict how structural modifications influence the binding pose and affinity of analogues within the H1 receptor binding pocket nih.govnih.gov. For instance, docking studies have supported the observation that this compound and desthis compound may adopt specific conformations when bound to the H1 receptor nih.gov. Computational methods can also be used to investigate the binding of this compound and its analogues to other targets like B0AT2 and ACE2, providing a deeper understanding of their polypharmacology researchgate.netnih.govsbgg.org.br.

Research into Enhanced Bioavailability Formulations

This compound's low aqueous solubility and significant first-pass metabolism after oral administration contribute to variable and sometimes poor oral bioavailability. nih.govjddtonline.infoturkjps.orgnih.gov Research efforts have been directed towards developing formulations that can overcome these limitations and enhance the bioavailability of this compound.

One significant approach involves improving the solubility and dissolution rate of this compound. Solid dispersion techniques have been widely investigated for this purpose. Studies have explored the use of various hydrophilic carriers, such as β-cyclodextrin, Poloxamer 407, PVP K30, PEG 6000, and Gelucire 44/14 and 50/13. nih.govbiotech-asia.orgsphinxsai.comwisdomlib.orgsphinxsai.com For instance, complexation with β-cyclodextrin using methods like kneading has shown enhanced solubility and faster disintegration times in fast-dissolving tablet formulations. biotech-asia.org Research using natural solid dispersions with hydrophilic natural polymers like sodium alginate, hyaluronic acid, and xyloglucan also demonstrated improved solubility and dissolution rates compared to pure this compound. nih.gov One study reported a 430-fold increase in solubility with a solid dispersion using β-cyclodextrin compared to other carriers. sphinxsai.comsphinxsai.com Another study utilizing Gelucire 44/14 at a 1:3 ratio (drug to carrier) achieved nearly complete drug release within 15 minutes in in vitro dissolution studies, significantly higher than the release from the pure drug. wisdomlib.org

Nanotechnology-based approaches have also been explored to enhance this compound's bioavailability. Nanocrystal formulations have been developed to increase the saturation solubility and improve the dissolution rate. nih.gov One study prepared this compound nanocrystals using high-speed shear-high pressure homogenization followed by freeze-drying, which were then incorporated into tablets. nih.gov The nanocrystal tablets showed significantly increased saturation solubility in various pH buffers compared to the crude drug. nih.gov Pharmacokinetic studies in rats demonstrated that the area under the curve (AUC) for the nanocrystal tablets was substantially higher than that of raw tablets and commercial tablets, indicating improved oral bioavailability. nih.gov

Another avenue of research focuses on solid dispersion tablets using modified natural gums. A study investigating solid dispersion tablets of this compound with modified Ziziphus spina-christi gum (MZG) as a carrier showed a significant increase in this compound solubility (51-fold). scilit.com Pharmacokinetic studies in albino Wistar rats revealed a considerable enhancement in bioavailability, with approximately 6-fold and 10-fold increases compared to MZG-free and commercial this compound tablets, respectively. scilit.com

The following table summarizes some research findings on solubility enhancement using different carriers:

Note: Solubility enhancement values are approximate and based on reported findings in the sources.

Investigation of Alternative Delivery Routes (e.g., transbuccal)

To bypass the extensive first-pass hepatic metabolism associated with oral administration, alternative routes of delivery for this compound have been investigated. jddtonline.infopharmreports.com These routes aim to deliver the drug directly into the systemic circulation or to the site of action, potentially improving bioavailability and reducing dose variability.

The nasal route has been explored for this compound delivery, particularly for the treatment of allergic rhinitis. jddtonline.infopharmreports.com Intranasal mucoadhesive gels have been developed to enhance bioavailability by prolonging retention at the nasal site and potentially bypassing first-pass metabolism. jddtonline.info One study formulated an intranasal mucoadhesive gel using Poloxamer 407 and Carbopol 934, demonstrating sustained drug release in vitro and potential for improved bioavailability. jddtonline.info Nanoparticle-loaded thermosensitive nasal in-situ gels have also been investigated. pharmreports.com Pharmacokinetic studies in rabbits showed a significant improvement in bioavailability (six-fold) with nanoparticle-loaded thermosensitive in-situ gels compared to an oral solution. pharmreports.com

Transbuccal delivery, administering the drug through the buccal mucosa, is another alternative route that offers the potential to avoid first-pass metabolism and gastrointestinal degradation. nih.govunesp.brjrespharm.com Research has focused on developing mucoadhesive formulations that can adhere to the buccal mucosa and facilitate drug permeation. nih.govjrespharm.com Transfersomal gels for transbuccal delivery of this compound have been developed and evaluated. nih.govresearchgate.netnih.govtandfonline.com Transfersomes are ultra-deformable vesicles that can enhance drug penetration across biological membranes. nih.gov A study investigating a transfersomal gel formulation reported improved ex vivo permeation across chicken pouch buccal mucosa and in vitro release compared to a control gel. nih.govresearchgate.net Pharmacokinetic studies in human volunteers showed that the bioavailability of the transfersomal gel was comparable to oral tablets, but significantly reduced inter-individual variability in pharmacokinetic parameters (Cmax and AUC). nih.govresearchgate.netnih.govtandfonline.com

Buccoadhesive films have also been explored for transbuccal delivery. jrespharm.comresearchgate.net These films are designed to adhere to the buccal mucosa, providing a prolonged release of the drug and potentially enhancing absorption. jrespharm.com Electrospun nanofiber films loaded with this compound have been developed for buccal delivery, aiming to improve drug solubility, dissolution, and transbuccal permeation. jrespharm.com In vitro studies using goat buccal mucosa showed enhanced transbuccal permeability of this compound from the nanofiber film. jrespharm.com

Sublingual administration, a specific type of oral mucosal delivery, has also been investigated for this compound. nih.govresearchgate.net Sublingual delivery allows for rapid absorption into the systemic circulation, bypassing first-pass metabolism. unesp.brnih.gov Fast-dissolving thin films for sublingual administration of this compound have been developed, often incorporating co-amorphous systems with substances like citric acid to enhance solubility and dissolution in the oral cavity. nih.govresearchgate.net Studies have shown that such formulations can achieve rapid drug release, suggesting the potential for a faster onset of action and improved bioavailability by avoiding the first-pass effect. nih.govresearchgate.net

Note: This table provides a summary of research findings and does not represent clinical efficacy or approved uses.

Assessment of Antihistaminic Activity in Guinea Pigs

Studies in guinea pigs have provided insights into the antihistaminic potency of this compound. In models of aerosol histamine-induced bronchospasm, this compound demonstrated antihistaminic activity, although some studies indicated it was less potent compared to other second-generation antihistamines like ebastine and cetirizine in this specific model. thieme-connect.com For instance, in one study, the median effective dose (ED50) for this compound against aerosol histamine-induced bronchospasm in guinea pigs was three-fold higher than that of ebastine and cetirizine. thieme-connect.com However, orally administered desthis compound, an active metabolite of this compound, was found to be 2.5 to 4 times more potent than this compound in inhibiting histamine-induced lethality in guinea pigs and blocking histamine-induced increases in nasal microvascular permeability. researchgate.netthieme-connect.comeuropa.eu The duration of the antihistaminic effect in guinea pigs was reported to be around 19 hours for this compound. thieme-connect.com

Investigation of Anticholinergic Effects in Animal Models

Preclinical studies in animal models have indicated that this compound exhibits little to no activity at acetylcholine receptors and is inactive in models designed to assess anticholinergic effects. researchgate.net Desthis compound also showed some competitive antagonistic properties at muscarinic M1 and M2 receptors in vitro, but these interactions had low affinity and did not translate into in vivo activity in animal models, such as protecting against physostigmine-induced cholinergic death in rats or showing activity against oxotremorine-induced hypothermia, tremor, or pilocarpine-induced salivation in mice. europa.euportico.org This suggests a selectivity for histamine H1 receptors over muscarinic receptors in vivo. portico.org

Studies on Skeletal System Effects in Rats

Studies investigating the effects of this compound on the skeletal system in rats have been conducted. In young, rapidly growing male Wistar rats, this compound administered orally at lower doses (0.5 and 5 mg/kg daily for 4 weeks) did not significantly affect the skeletal system. mdpi.comresearchgate.netnih.govnih.gov However, at a high dose (50 mg/kg daily), this compound slightly but significantly affected the development of the skeletal system. mdpi.comresearchgate.netnih.govnih.gov This high dose was associated with a decrease in femoral length and an increase in the content of calcium and phosphorus in the bone mineral of the L-4 vertebra. nih.govnih.gov It is noted that the effects observed at the highest dose might be attributable to toxicity rather than solely an effect on H1-receptors, given the decreased body mass gain and increased liver mass observed at this dose. mdpi.comnih.gov

Seasonal Allergic Rhinitis (Hay Fever)

This compound has shown significant clinical efficacy in the treatment of seasonal allergic rhinitis (SAR), commonly known as hay fever. Studies have consistently shown that this compound provides relief from symptoms such as sneezing, rhinorrhea (runny nose), nasal itching, and itching/burning eyes in patients with SAR. nih.govwithpower.comtheindependentpharmacy.co.ukclaritin.comdroracle.ai

Comparison with Placebo and Other Antihistamines

Numerous randomized, double-blind, placebo-controlled clinical trials have compared the efficacy of this compound with placebo and other antihistamines in the treatment of SAR.

Comparison with Placebo: Studies have shown that this compound is significantly more effective than placebo in reducing the severity of SAR symptoms. nih.govresearchgate.netnih.govmedscape.comdrugs.com For example, in a 14-day study involving 317 patients, this compound treatment resulted in a 46% decrease in mean total scores of combined nasal and nonnasal symptoms from baseline, compared to a 35% decrease with placebo, a statistically significant difference (p = 0.03). nih.gov Another study showed that more this compound-treated subjects (65%) had no symptoms or mild rhinitis at the end of the study compared to placebo subjects (49%). nih.gov

Interactive Table 1: Change in Total Symptom Scores in SAR (this compound vs. Placebo)

Comparison with Other Antihistamines: Comparisons with other second-generation antihistamines have yielded varied results, with some studies showing comparable efficacy and others suggesting differences in onset of action or effectiveness for specific symptoms.

Terfenadine: Studies comparing this compound with terfenadine have generally found comparable efficacy in controlling SAR symptoms. nih.govresearchgate.netnih.gov In one study, both this compound and terfenadine showed a statistically greater reduction in symptom scores compared to placebo and were not statistically different from each other. researchgate.netnih.gov However, one study focusing on the end of the 24-hour dosing period suggested that this compound might control symptoms more effectively than terfenadine in the later hours. nih.gov

Astemizole: A double-blind study comparing this compound, astemizole, and placebo in hay fever patients found that this compound was statistically superior to placebo on the third day of treatment, while astemizole and placebo showed no significant differences in symptom ratings at that time point. nih.gov this compound was also reported to have a significantly earlier onset of action than astemizole with comparable efficacy over the study period. nih.gov Another study comparing this compound and astemizole in perennial allergic rhinitis found significant symptom improvement from the third day for both drugs, with no significant difference between them, although this compound led to a greater symptom reduction. researchgate.net

Cetirizine: Comparisons between this compound and cetirizine in SAR have shown inconsistent results. Some studies have found comparable efficacy between the two drugs in alleviating symptoms like sneezing, runny nose, itchy or watery eyes. withpower.comwithpower.com However, other studies have suggested differences. A field study reported that cetirizine produced significantly greater mean reductions in major and total symptom complex severity scores than this compound at various evaluation periods and had a more rapid onset of action. nih.gov Conversely, a study in children aged 6-11 years with SAR found no statistically significant difference in symptom improvement between this compound and cetirizine compared to placebo. researchgate.netingentaconnect.com Another study indicated that while both were effective, cetirizine might be slightly more effective in reducing symptoms, though the difference was not always statistically significant.

Fexofenadine: Studies comparing this compound and fexofenadine for SAR have also shown mixed results. Both have been shown to provide significant relief compared to placebo. researchgate.netmedscape.com Some studies found similar reductions in symptom scores with both agents. researchgate.netmedscape.com However, one study reported that this compound demonstrated a statistically greater percentage reduction in symptom scores in the initial assessments and achieved significance versus fexofenadine as early as 12 hours after the first dose, with a significantly earlier time to 25% and maximum symptom reduction. researchgate.netmedscape.com Conversely, another study evaluating nonresponders to initial therapy found that more patients had moderate, marked, or complete relief after switching to this compound than after switching to fexofenadine. nih.gov

Interactive Table 2: Comparative Efficacy of this compound vs. Other Antihistamines in SAR (Illustrative Data from Selected Studies)

Symptom Score Reductions (Nasal and Ocular)

Clinical trials have demonstrated that this compound is effective in reducing both nasal and ocular symptoms associated with allergic rhinitis. Studies have evaluated symptom severity using scoring systems that assess sneezing, nasal discharge, nasal congestion, nasal itching, ocular itching, burning, and erythema.

In a study evaluating this compound in pediatric patients with severe perennial allergic rhinitis, a combination treatment including this compound significantly reduced the total nasal and ocular symptom score from a baseline of 11.4 (±2.1) to 2.9 (±2.4) after 5 days of treatment (P < 0.01). Significant reductions were also observed for individual symptoms such as sneezing, nasal pruritus, nasal congestion, rhinorrhea, postnasal drip, and ocular erythema and pruritus (P < 0.01). nih.govnih.gov

Another study comparing this compound with fexofenadine and placebo in adults with seasonal allergic rhinitis showed that both this compound and fexofenadine provided significant symptom relief compared to placebo. This compound demonstrated a statistically greater percentage reduction in AM and PM reflective total symptom scores in several assessments during the initial days of treatment compared to fexofenadine. medscape.com

However, a network meta-analysis evaluating the efficacy of different oral H1 antihistamines for allergic rhinitis suggested that this compound 10 mg was ranked the lowest in symptom score reductions compared to other antihistamines like rupatadine and levocetirizine, although it was still more effective than placebo.

Here is a summary of symptom score reductions observed in a pediatric perennial allergic rhinitis study:

Perennial Allergic Rhinitis

This compound has been evaluated for its efficacy in treating perennial allergic rhinitis (PAR). Studies have compared this compound to placebo and other antihistamines in this population.

A multicenter, double-blind study comparing mizolastine and this compound in PAR patients reported comparable symptom relief with both treatments over four weeks. This compound resulted in a 61.3% decrease in total nasal score, a 76.4% decrease in total ocular score, and a 64.8% decrease in global total score. rhinologyjournal.com

Urticaria (Hives) and Pruritus

This compound is also indicated for the treatment of urticaria (hives) and pruritus (itching) associated with various skin conditions. wikipedia.orgclinicaltrials.eu Its efficacy in managing these symptoms has been investigated in clinical trials.

This compound is considered a low-sedation anti-H1 antihistamine and is part of the first-line pharmacotherapy for chronic urticaria. medscape.com Studies have evaluated its effectiveness in reducing the intensity of hives and pruritus in patients with chronic urticaria. medscape.comnih.gov While some studies suggest other antihistamines like cetirizine or levocetirizine might show greater suppression of histamine-induced skin reactions in comparative crossover studies, this compound has demonstrated clinical efficacy in reducing urticarial symptoms. medscape.comnih.gov

Several trials have compared this compound to other antihistamines in patients with chronic urticaria, with outcomes often including the assessment of pruritus severity and the number of hives. nih.govcochranelibrary.com For example, a review of desthis compound (this compound's active metabolite) in chronic idiopathic urticaria highlighted that it improved the severity of pruritus and the number of hives in randomized, placebo-controlled trials. openaccessjournals.com Given that desthis compound is the primary active metabolite, these findings are relevant to the efficacy of this compound.

Studies on Onset and Duration of Action

Studies have investigated how quickly this compound starts to relieve symptoms and how long its effects last. This compound is known for its rapid onset of action and provides 24-hour symptom relief with once-daily dosing. medscape.commedsafe.govt.nz

Human skin wheal studies have shown that the antihistaminic effect of a single 10 mg oral dose of this compound begins within 1 to 3 hours, reaches a maximum effect at 8 to 12 hours, and lasts for more than 24 hours. fda.gov

In clinical studies for seasonal allergic rhinitis, symptom relief with this compound can begin in as little as 10 to 20 minutes after the first dose, with a mean onset of relief reported at 27 minutes in some patients. By 45 minutes, most patients should experience relief. medsafe.govt.nz A post hoc analysis of a study in an Environmental Exposure Unit reported an onset of action of 75 minutes for the relief of both nasal and ocular symptoms with this compound tablets. nih.govnih.gov This contrasts with some older studies that suggested a longer onset (around 180 minutes) for encapsulated formulations of this compound. nih.govnih.gov

The mean elimination half-life of this compound is approximately 8.4 hours, while its active metabolite, desthis compound, has a longer mean elimination half-life of about 28 hours, contributing to the prolonged duration of action. medsafe.govt.nzfda.gov

This compound and Montelukast Combination for Allergic Rhinitis

The combination of this compound, an antihistamine, and montelukast, a leukotriene receptor antagonist, has been investigated for the treatment of allergic rhinitis. The rationale behind this combination is to target multiple inflammatory pathways involved in allergic responses. nih.gov

A systematic review and meta-analysis evaluated the efficacy of this compound combined with montelukast for allergic rhinitis. The pooled results indicated that the combination significantly reduced total nasal symptom scores (TNSS) compared to this compound monotherapy, montelukast monotherapy, or placebo. nih.govresearchgate.netresearchgate.net

Studies have compared the combination therapy to monotherapy with either drug and to placebo in patients with seasonal allergic rhinitis. nih.govnih.gov

Here is a summary of the effect of this compound-Montelukast combination on Total Nasal Symptom Scores (TNSS) compared to monotherapy and placebo from a meta-analysis:

The meta-analysis also showed that the combination therapy significantly improved specific nasal symptoms such as nasal congestion, nasal itching, nasal sneezing, and nasal rhinorrhea compared to this compound alone. Compared to montelukast alone, the combination significantly improved nasal itching and nasal sneezing. nih.govresearchgate.netresearchgate.net

Synergistic or Additive Therapeutic Effects

The combination of this compound and montelukast is proposed to yield additive therapeutic effects by targeting different mediators of the allergic response: histamine (blocked by this compound) and leukotrienes (blocked by montelukast). nih.gov

The observed benefits of the combination therapy over monotherapy in reducing symptom scores and improving quality of life suggest at least additive, if not synergistic, effects by addressing multiple facets of the complex inflammatory process in allergic rhinitis. nih.govbioworld.come-century.us

Randomized Controlled Trials

Randomized controlled trials (RCTs) are a cornerstone of clinical research for evaluating the efficacy of interventions like this compound. These studies involve randomly assigning participants to receive either this compound, a comparator treatment, or a placebo, minimizing bias and allowing for robust comparisons.

Several RCTs have demonstrated the efficacy of this compound in treating seasonal allergic rhinitis. For instance, a 14-day double-blind, randomized study involving 317 patients with seasonal allergic rhinitis compared this compound (10 mg once daily), terfenadine, and placebo. At the study's end, the mean total scores for combined nasal and nonnasal symptoms showed improvements of 46% for this compound, 44% for terfenadine, and 35% for placebo from baseline. The difference between this compound and placebo treatment was statistically significant (p = 0.03). This compound was particularly effective in relieving nasal discharge, sneezing, and itching/burning eyes compared to placebo. nih.gov Another double-blind, placebo-controlled study in patients with seasonal allergic rhinitis found that this compound induced significant relief of nasal symptoms compared to placebo, with significant superiority observed after 3 days of treatment. nih.gov

Comparisons with other antihistamines in RCTs have yielded varied results. One study comparing this compound (10 mg) and fexofenadine (60 mg twice daily) to placebo for 7 days in patients with seasonal allergic rhinitis found that both active treatments provided significant symptom relief compared to placebo. medscape.com this compound demonstrated a statistically greater percentage reduction in morning and evening reflective total symptom severity scores in four of the initial five assessments compared to fexofenadine, achieving significance as early as 12 hours after the first dose. medscape.com Median times to a 25% and maximum reduction in morning reflective total symptom severity scores also occurred significantly earlier with this compound. medscape.com

However, other RCTs have shown comparable or, in some specific measures, inferior efficacy for this compound compared to other second-generation antihistamines. A study comparing ebastine (20 mg and 10 mg) and this compound (10 mg) to placebo over 4 weeks in patients with seasonal allergic rhinitis found that ebastine 20 mg showed larger mean reductions from baseline in most rhinitis symptom scores than this compound 10 mg. jiaci.org Sustained efficacy over placebo was most frequently observed with ebastine 20 mg, while this compound 10 mg did not provide a statistically significant sustained effect in this particular study. jiaci.org In a study involving children aged 6-11 years with seasonal allergic rhinitis, symptom improvement was not significantly different between the this compound 10 mg group and the placebo group over 14 days. researchgate.net

Data from an RCT comparing this compound, terfenadine, and placebo in seasonal allergic rhinitis:

Source: Adapted from PubMed nih.gov

Meta-Analyses and Systematic Reviews of Efficacy

A systematic review and network meta-analysis evaluating the efficacy of different oral H1 antihistamine treatments for allergic rhinitis included 18 eligible randomized controlled studies with a total of 9419 participants. scielo.br This analysis found that all included antihistamine treatments outperformed placebo in reducing total symptom scores and individual symptom scores. scielo.br However, according to the Surface Under the Cumulative Ranking Curves (SUCRA) analysis, this compound 10 mg was ranked the lowest in reducing each symptom score compared to other antihistamines included in the analysis, besides placebo. scielo.br This suggests that while effective compared to placebo, this compound 10 mg may have inferior efficacy compared to some other oral H1 antihistamines for allergic rhinitis symptoms based on this specific network meta-analysis.

Meta-analyses have also investigated this compound in combination therapies. A systematic review and meta-analysis of this compound combined with montelukast for allergic rhinitis included 23 studies with 4,902 participants. nih.govresearchgate.netnih.gov Pooled results showed that the combination of this compound-montelukast significantly reduced total nasal symptom scores compared to this compound alone, montelukast alone, or placebo. nih.govresearchgate.netnih.gov The combination therapy also significantly improved nasal congestion, nasal itching, nasal sneezing, nasal rhinorrhea, and rhinoconjunctivitis quality of life questionnaire scores compared to this compound monotherapy. nih.govresearchgate.netnih.gov

Assessment of Quality of Life in Patients

The impact of allergic rhinitis and its treatment on patients' quality of life is an important outcome measure in clinical trials. Quality of life assessments evaluate how symptoms affect daily activities, sleep, and emotional well-being.

Studies have utilized tools such as the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) to assess the effect of this compound on health-related quality of life. researchgate.netijbcp.comnih.gov A prospective randomized double-blinded study compared the impact on quality of life of bilastine 20 mg versus this compound 10 mg in 73 patients with allergic rhinitis over 10 days. researchgate.netnih.govclinconnect.io Both treatments significantly reduced RQLQm scores after 10 days (p < 0.001), indicating an improvement in quality of life. researchgate.netnih.gov However, there was no statistically significant difference in the quality of life improvement between the two treatment groups (p > 0.05). researchgate.netnih.gov This suggests that both this compound and bilastine were equivalently effective in improving health-related quality of life in this study population. researchgate.netnih.gov

Another study assessing quality of life using RQLQ in patients treated with different antihistamines, including this compound, found that patients across all tested groups showed an improved perception of their health-related quality of life. ijbcp.com Significant improvements were reported in nasal symptoms, daily activities, sleep, and psychological impact. ijbcp.com

High-Performance Liquid Chromatography (HPLC)

HPLC is a versatile and widely applied technique for the analysis of this compound in various samples, including raw materials, pharmaceutical formulations, and biological fluids. actascientific.comijbpas.comajchem-a.combch.rofarmaciajournal.comneuroquantology.comnih.govresearchgate.netnuph.edu.uarjptonline.org HPLC methods offer advantages such as accuracy, precision, and reproducibility. ijbpas.combch.roneuroquantology.com

Different stationary phases and mobile phases have been explored to achieve optimal separation of this compound. Reversed-phase HPLC (RP-HPLC) is a common mode used for this compound analysis. ijbpas.combch.roneuroquantology.comnih.govresearchgate.netrjptonline.org

HPLC-UV Methodologies

HPLC coupled with Ultraviolet (UV) detection is a frequently used method for the quantitative determination of this compound. ijbpas.combch.rofarmaciajournal.comneuroquantology.comnih.govresearchgate.netnuph.edu.uarjptonline.org This approach utilizes the UV absorbance properties of this compound for its detection and quantification after chromatographic separation.

Several HPLC-UV methods have been developed and validated for the estimation of this compound in tablets and bulk drug. One method employed a reversed-phase C8 column with a mobile phase consisting of methanol, acetonitrile, and a pH 3.5 buffer, with detection at 215 nm. This method showed linearity in the range of 20-160 µg/ml with a correlation coefficient of 0.999 and a retention time of 4.358 min. ijbpas.com Another RP-HPLC method used a C18 column and a mobile phase of acetate buffer solution/methanol (15/85, v/v) with UV detection at 248 nm. bch.roresearchgate.net This method was validated for linearity, detection limit, quantitation limit, precision, and accuracy, showing good agreement with ICH guidelines. bch.roresearchgate.net A DAD-HPLC method for this compound assay demonstrated linearity from 0.5 µg/mL to 9.0 µg/mL and good precision and accuracy with detection at 280 nm. farmaciajournal.com Another RP-HPLC method utilized a C8 column and UV detection at 247 nm, showing linearity between 5-50 µg/ml with a correlation coefficient of 0.999. neuroquantology.com

Table 1 summarizes some reported HPLC-UV methods for this compound analysis.

HPLC-MS/MS Methodologies

HPLC coupled with tandem Mass Spectrometry (MS/MS) provides enhanced sensitivity and selectivity for this compound analysis, particularly in complex matrices. nih.govrjptonline.orgijpsonline.comnovartis.com This technique is often used for the determination of this compound and its metabolites in biological samples.

An LC-MS/MS method was developed and validated for the quantitative analysis of this compound in human dried blood spot (DBS) samples. novartis.comnih.gov The method involved extracting the drug from DBS samples using aqueous methanol and chromatography on a C18 column with isocratic elution, followed by MS/MS detection. novartis.comnih.gov This method was validated over a dynamic range of 0.200-20.0 ng/ml with correlation coefficients of 0.990 or better. nih.gov

Another LC-MS/MS method for the simultaneous quantitation of this compound and its metabolite desthis compound in beagle plasma utilized liquid-liquid extraction and separation on a C8 column with acetonitrile and ammonium formate as the mobile phase. nih.govtandfonline.com This method showed good linearity over the concentration ranges of 0.008-24 ng/mL for this compound and 0.8-800 ng/mL for desthis compound. nih.govtandfonline.com

An HPLC-ESI-MS method for determining this compound in human plasma used reversed-phase HPLC with electrospray ionization (ESI) mass spectrometry in single ion monitoring (SIM) mode. ingentaconnect.comnih.gov The method involved liquid-liquid extraction and separation on an ODS-3 column. ingentaconnect.comnih.gov Linearity was observed over the range of 0.2–100 ng/ml, and the extraction recovery was reported to be over 80%. ingentaconnect.comnih.gov

Liquid Chromatography-Mass Spectrometry (LC-MS/MS) for Bioanalysis

LC-MS/MS is a powerful tool for the bioanalysis of this compound, allowing for sensitive and specific detection in biological matrices such as plasma and blood. ijbpas.comijpsonline.comnovartis.com The high sensitivity of LC-MS/MS is particularly advantageous for quantifying low concentrations of this compound in biological samples for pharmacokinetic studies. novartis.comnih.govnih.govtandfonline.comingentaconnect.comnih.govshimadzu.co.krbjmu.edu.cn

A sensitive LC-MS/MS method was developed for the quantitation of this compound from plasma, achieving low ppt level quantitation using a triple quadrupole mass spectrometer with a heated electrospray ionization (ESI) interface. shimadzu.co.kr This method involved protein precipitation from plasma using cold acetonitrile. shimadzu.co.kr

LC-MS/MS methods have been successfully applied to determine this compound levels in human dried blood spot samples and beagle plasma, demonstrating good accuracy and precision. novartis.comnih.govnih.govtandfonline.com These methods are crucial for supporting pharmacokinetic studies and understanding the behavior of this compound in biological systems. novartis.comnih.govnih.govtandfonline.comingentaconnect.comnih.gov

UV-Spectrophotometry

UV-Spectrophotometry is based on the principle that this compound absorbs UV light at specific wavelengths. ijbpas.comrjptonline.orgnovartis.comasianpubs.orgresearchgate.netajrconline.orgasianpubs.orgrjptonline.org This technique is often used for routine quality control analysis of this compound in tablets and raw materials. ijbpas.combch.roasianpubs.org

Several UV-spectrophotometric methods have been developed for this compound estimation, with reported maximum absorbance wavelengths () varying depending on the solvent or conditions used. Some methods report at 246 nm asianpubs.orgresearchgate.net, 247 nm ajrconline.orgrjptonline.org, 275 nm actascientific.comresearchgate.netasianpubs.org, and 280 nm rjptonline.org. Beer-Lambert's law has been reported to be obeyed over specific concentration ranges in different methods. actascientific.comasianpubs.orgresearchgate.netajrconline.orgasianpubs.orgrjptonline.org

One UV-spectrophotometric method for this compound in tablets reported a at 246 nm and linearity in the range of 0-25 µg/mL. asianpubs.orgresearchgate.net Another method found the absorption maximum at 275 nm with percentage recovery ranging from 99.982 to 101.4908% in pharmaceutical dosage forms. researchgate.netasianpubs.org A method using 0.1N HCl as solvent reported a at 275 nm and linearity between 4-40 µg/mL with a correlation coefficient of 0.9999. asianpubs.org UV spectrophotometric methods have also been developed based on the reaction of this compound with specific reagents to form a chromogen that can be measured spectrophotometrically. ijpsonline.comekb.eguniv-ovidius.ro For instance, a method based on the reaction of this compound with potassium tetraiodomercuriate in the presence of hydrochloric acid showed a maximum absorbance at 380 nm. univ-ovidius.ro Another method involved the reaction of this compound with potassium iodide in the presence of hydrochloric acid, yielding a chromogen with absorption at 370 nm. ijpsonline.com

Table 2 summarizes some reported UV-Spectrophotometric methods for this compound analysis.

Cathodic Stripping Voltammetry (CSV)

Cathodic Stripping Voltammetry (CSV) is a sensitive electrochemical technique utilized for the determination of electroactive compounds like this compound. CSV involves an initial accumulation step where the analyte is deposited onto the electrode surface, followed by a stripping step where the accumulated analyte is reduced (in the case of cathodic stripping) and the resulting current is measured. This preconcentration step enhances the sensitivity of the method.

Research has demonstrated the application of CSV for the determination of this compound in various samples, including pharmaceutical formulations and biological fluids such as urine and human plasma researchgate.netnih.govresearchgate.net. This compound has been shown to be electro-active at mercury electrodes, exhibiting a reduction wave corresponding to the saturation of the carbon-nitrogen double bond in its pyridine ring at pH values greater than or equal to 6 researchgate.net. Studies using a bismuth film electrode (BiFE) have also investigated the electrochemical behavior of this compound, observing an irreversible reduction peak around -1.48 V in a specific buffer solution containing a cationic surfactant researchgate.netbatman.edu.tr. Optimized conditions for cathodic adsorptive stripping voltammetry have been reported, including the use of a sodium hydroxide supporting electrolyte, a specific accumulation potential and time, and a defined scan rate and pulse amplitude nih.gov.

X-ray Photoelectron Spectroscopy

X-ray Photoelectron Spectroscopy (XPS), also known as Electron Spectroscopy for Chemical Analysis (ESCA), is a surface-sensitive quantitative spectroscopic technique that measures the elemental composition, empirical formula, chemical state, and electronic state of the elements within a material. Its application in this compound research is primarily focused on characterizing the surface chemistry of solid forms, such as tablets.

XPS analysis of this compound tablets has been conducted to identify the elements present on the surface. These studies have confirmed the presence of carbon, oxygen, nitrogen, and chlorine, which are constituent elements of the this compound molecule aip.orgaip.orgresearchgate.net. However, carbon and oxygen signals can also originate from excipients present in the tablet formulation aip.orgaip.org. The detection of sodium in XPS analysis of tablets has been associated with excipients aip.orgaip.org. Furthermore, XPS can provide information about the chemical states of these elements. For instance, analysis of the carbon 1s spectrum can reveal different carbon species, including those single-bonded to nitrogen or oxygen, and those double or single-bonded to oxygen in ester groups aip.org. The ratio of nitrogen to chlorine atomic percentages determined by XPS has been shown to correspond to the expected ratio based on the chemical formula of this compound, helping to confirm the presence of the active compound on the surface aip.org.

Continuous Flow Injection Analysis (CFIA)

Continuous Flow Injection Analysis (CFIA) is an automated analytical technique that involves the injection of a liquid sample into a continuous flow of a carrier stream. The injected sample disperses and reacts with reagents in the stream, and the resulting product is detected downstream, often spectrophotometrically or electrochemically. CFIA offers advantages such as high sample throughput, reduced reagent consumption, and ease of automation ajol.info.

CFIA has been developed and applied for the quantification of this compound, particularly in pharmaceutical formulations ajchem-a.comajchem-a.comresearchgate.net. One approach involves the precipitation of this compound through a reaction, and the resulting precipitate is then analyzed using a detector that measures the reduction of light ajchem-a.comajchem-a.com. A specific analyzer, the NAG_4SX3_3D Analyzer, has been used in conjunction with CFIA for the turbidimetric measurement of this compound, where a white precipitate is formed by mixing this compound with 3,5-dinitrosalicylic acid ajchem-a.comajchem-a.comresearchgate.net. The signal obtained from this process is acquired using a flow chamber within the analyzer ajchem-a.com. The flow rate is a critical parameter in CFIA, affecting peak response and dispersion ajchem-a.com.

Limit of Detection (LOD) and Limit of Quantification (LOQ)

The Limit of Detection (LOD) is defined as the lowest concentration of an analyte that can be reliably detected, though not necessarily quantified, under the stated experimental conditions. The Limit of Quantification (LOQ) is the lowest concentration of an analyte that can be quantified with acceptable accuracy and precision. These parameters are essential for demonstrating the sensitivity of an analytical method for this compound research.

LOD and LOQ values for this compound vary depending on the analytical technique employed and the matrix being analyzed. For instance, a CFIA method using a specific analyzer reported an LOD of 611.076 ng and an LOQ of 129 μg ajchem-a.comajchem-a.com. An HPLC method with fluorescence detection for analyzing this compound in human serum reported significantly lower values, with an LOD of 0.07 ng/mL and an LOQ of 0.2 ng/mL akjournals.com. Derivative spectrophotometry methods have also reported LOD and LOQ values for this compound in the microgram per milliliter range researchgate.netresearchgate.net. Cathodic stripping voltammetry using a bismuth film electrode provided an LOD of 0.12 µM (equivalent to 0.046 mg/mL) researchgate.net. Another cathodic adsorptive stripping voltammetry method reported LODs in the nanomolar range for pharmaceutical formulations and human plasma nih.gov.

Here is an interactive table summarizing some reported LOD and LOQ values for this compound using different analytical techniques:

Linearity and Correlation Coefficients

Linearity is a measure of an analytical method's ability to elicit test results that are directly proportional to the concentration of the analyte within a defined range. This relationship is typically established by constructing a calibration curve, where the instrument response (e.g., peak area, absorbance, current) is plotted against the corresponding analyte concentration. The linearity is assessed by calculating the correlation coefficient (r or R2) of the regression line. A correlation coefficient close to 1 indicates a strong linear relationship.

Research on this compound analysis consistently involves the evaluation of method linearity. Various studies report linear ranges and correlation coefficients for different techniques. For a CFIA method, a linear range with a correlation coefficient (r) of 0.9989 and linearity (R2) of 99.79% was observed ajchem-a.comajchem-a.com. HPLC methods have demonstrated good linearity over specific concentration ranges, with correlation coefficients typically exceeding 0.999 ijbpas.comakjournals.comneuroquantology.com. For instance, an RP-HPLC method showed linearity from 20-160 µg/mL with a correlation coefficient of 0.999 ijbpas.com. Another RP-HPLC method for API and formulations reported linearity in the range of 5-50 µg/mL with a correlation coefficient of 0.999 neuroquantology.com. A DAD-HPLC method showed linearity between 0.5 µg/mL and 9.0 µg/mL farmaciajournal.com. Spectrophotometric methods have also shown good linearity, with correlation coefficients close to 1 researchgate.netresearchgate.netasianpubs.org. For a derivative spectrophotometry method, R2 values of 0.99996 and 0.99978 were reported at different wavelengths researchgate.net. Cathodic stripping voltammetry using a BiFE showed a good linear relationship with a correlation coefficient (r) of 0.998 over a specific concentration range researchgate.net.

Here is an interactive table presenting some reported linearity ranges and correlation coefficients for this compound analysis:

Extraction Recovery and Precision

The accurate and precise determination of this compound in various matrices, particularly biological fluids and pharmaceutical formulations, necessitates robust extraction procedures. Extraction recovery refers to the efficiency of the method in isolating the analyte from the sample matrix, while precision indicates the reproducibility of the results obtained from replicate analyses. Several analytical techniques, often coupled with chromatographic methods like High-Performance Liquid Chromatography (HPLC) and Liquid Chromatography-Mass Spectrometry (LC-MS), have been developed and validated for this compound analysis, with reported data on extraction recovery and precision.

Liquid-liquid extraction (LLE) is a commonly employed technique for the isolation of this compound from biological samples such as plasma or serum. One validated HPLC-ESI-MS method for this compound in human plasma reported an extraction recovery of more than 80%. ingentaconnect.com In this method, a simple liquid-liquid extraction was performed, followed by evaporation of the organic extract and reconstitution of the residue in the mobile phase for injection into the HPLC system. ingentaconnect.com The intra-assay and inter-assay precision of this method were reported to be within 12% relative standard deviation (RSD). ingentaconnect.com

Solid-phase extraction (SPE) is another widely used technique. A rapid HPLC method with fluorescence detection for this compound in human serum utilized a simple solid-phase extraction procedure. akjournals.com The mean absolute recovery of this compound using this SPE method ranged from 93.0% to 94.3% at different quality control levels (1, 5, and 10 ng/mL). akjournals.com The inter-day precision for this method ranged from 1.3% to 18.2%. akjournals.com

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) methods often offer enhanced sensitivity and selectivity for this compound analysis in complex matrices like plasma. One LC-MS/MS method for this compound in human plasma reported an average recovery of 102.685% after extraction. graphyonline.com Another study utilizing LC-MS/MS with protein precipitation for sample clean-up reported an extraction recovery of 101.56 ± 0.1% for this compound in spiked plasma samples. scielo.br This method demonstrated satisfactory extraction efficiency, proving both consistent and reproducible, which was attributed to the effectiveness of the protein precipitation procedure. scielo.br

Micellar HPLC has also been explored for this compound analysis, offering the advantage of potentially avoiding tedious extraction steps for biological fluids. nih.gov A validated micellar liquid chromatographic method for this compound in various matrices, including human urine, plasma, and breast milk, reported accuracy higher than 97% and intra- and inter-day precisions with relative standard deviations not exceeding 2%. nih.gov

For pharmaceutical formulations, different extraction procedures may be used depending on the dosage form. For instance, a validated RP-HPLC method for this compound in capsule dosage forms involved weighing and powdering tablets, followed by extraction with a diluent (methanol) and sonication. iajps.comijbpas.com The mean recovery for this method was reported as 99.5%, with intra-day and inter-day RSD values less than 1.0%, indicating good precision and accuracy for the determination of this compound in tablet formulations. iajps.com Another HPLC method for this compound in pharmaceutical preparations, using methanol as a solvent for extraction from powdered tablets, reported a percentage recovery range of 99.33-100.4% and system precision (RSD) of 1.92%. ijbpas.comfarmaciajournal.com

The precision of analytical methods for this compound is typically assessed through repeatability (intra-day) and intermediate precision (inter-day or between analysts). Reported RSD values for precision vary depending on the method and matrix. For example, an RP-HPLC method for this compound in pharmaceutical formulations showed intra-day and inter-day RSD values below 1.0%. iajps.com Another validated method for this compound in methanol reported a precision (RSD) of 0.295%. researchgate.net For biological samples, slightly higher RSD values may be observed, such as the intra-assay and inter-assay precision within 12% RSD reported for an HPLC-ESI-MS plasma assay ingentaconnect.com, or intra-batch and inter-batch precision (%CV) less than 9% for an LC-MS/MS method in human plasma oup.com.

Detailed research findings on extraction recovery and precision are often presented in validation studies for specific analytical methods. These studies typically involve analyzing quality control samples at different concentration levels and calculating the percentage recovery and relative standard deviation. The acceptance criteria for recovery and precision are often based on regulatory guidelines, such as those from the ICH or FDA.

Here are some examples of reported extraction recovery and precision data for this compound from various sources: