Tafenoquine

ANone: Tafenoquine, an 8-aminoquinoline antimalarial drug, exerts its activity against Plasmodium species by targeting the parasite's liver stage hypnozoites, effectively preventing relapse in vivax and ovale malaria. While its exact mechanism is not fully elucidated, research suggests it involves the production of oxidative metabolites that are detrimental to the parasite. [] These metabolites are thought to disrupt essential parasite functions, ultimately leading to parasite death. [, ]

ANone: While primarily recognized for its anti-relapse properties against P. vivax and P. ovale, studies demonstrate that this compound also exhibits transmission blocking activity against P. falciparum. [] Low doses of this compound administered to infected individuals were shown to significantly reduce both oocyst and sporozoite positivity rates in mosquitoes feeding on these individuals, ultimately decreasing transmission rates. []

ANone: The molecular formula of this compound succinate, the salt form commonly used in pharmaceutical formulations, is C24H28F3N3O3∙C4H6O4. Its molecular weight is 581.6 g/mol. [, ]

ANone: Various analytical techniques have been utilized for this compound characterization, including nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, mass spectrometry (MS), high-performance liquid chromatography (HPLC), and fluorimetry. [] These methods aid in confirming the drug's identity, purity, and stability.

ANone: Yes, computational chemistry studies have been performed on this compound, particularly in the context of pharmacokinetic/pharmacodynamic (PK/PD) modeling. This modeling helps understand the relationship between drug concentration and its effects, allowing researchers to optimize dosing regimens and predict potential drug interactions. []

ANone: While the research papers don't delve into specific SAR studies, it is understood that even minor structural modifications to this compound or related 8-aminoquinolines could significantly influence their pharmacological properties, including their antimalarial activity, potency, and potential for side effects.

ANone: Population pharmacokinetic studies conducted on this compound administered as both capsules and tablets revealed no clinically significant difference in relative bioavailability between the two formulations. [] This suggests that this compound exhibits good stability in both these commonly used oral dosage forms.

ANone: this compound exhibits a long elimination half-life of approximately 12.7 days. [] The typical values for the first-order absorption rate constant (Ka), clearance (CL/F), and volume of distribution (V/F) were determined to be 0.243 h−1, 0.056 liters/h/kg, and 23.7 liters/kg, respectively. []

ANone: While not explicitly mentioned in the provided research papers, 8-aminoquinolines like this compound are primarily metabolized in the liver and subsequently eliminated through feces. []

ANone: While CYP2D6 is known to play a crucial role in the metabolism of primaquine, studies on this compound have yielded conflicting results. Some research suggests that CYP2D6 activity might influence this compound's effectiveness in preventing P. vivax relapses, while other studies indicate that CYP2D6 status does not significantly affect plasma this compound concentrations or its anti-relapse efficacy. [, ]

ANone: The in vitro activity of this compound has been evaluated using various methods, including the inhibition of schizont maturation assay, which measures the drug's ability to prevent the maturation of Plasmodium falciparum parasites in red blood cells. [, ]

ANone: this compound demonstrates promising in vitro activity against chloroquine-resistant strains of P. falciparum. Studies have shown that this compound maintains its efficacy even in regions where chloroquine resistance is prevalent, highlighting its potential as a valuable treatment option in such areas. [, ]

ANone: Mice infected with Babesia microti, a parasite causing babesiosis, have been successfully utilized as an animal model to investigate the efficacy and pharmacokinetics of this compound. Studies have shown that a single oral dose of this compound in these mice effectively reduces parasitemia, mimicking its activity against Plasmodium species in humans. []

ANone: Several clinical trials have demonstrated the efficacy and safety of this compound for malaria prophylaxis. Notably, a Phase III trial involving Australian soldiers deployed to East Timor showed that weekly this compound prophylaxis was as effective as mefloquine in preventing malaria. [] Similarly, trials in Ghana, Kenya, and Thailand confirmed the efficacy of different weekly this compound regimens in preventing P. falciparum infection. [, , ]

ANone: Clinical trials have shown that a single dose of this compound (300 mg) is as effective as a 14-day course of primaquine (15 mg daily) in preventing P. vivax relapse. [, ] This finding highlights the potential of this compound to improve patient adherence and simplify treatment regimens for P. vivax malaria.

ANone: While there have been no documented cases of clinical resistance to this compound, the potential for resistance development remains a concern. This concern is particularly relevant given the drug's long half-life, which could allow parasites prolonged exposure to subtherapeutic drug concentrations, potentially favoring the selection of resistant strains. []

ANone: this compound administration has been associated with generally mild and transient side effects. The most common ones include gastrointestinal disturbances such as nausea, vomiting, and diarrhea. [, ]

ANone: A randomized, double-blind, placebo-controlled study assessed the long-term ophthalmic and renal effects of this compound. The study found no clinically significant differences in night vision or other ophthalmic indices between the this compound and placebo groups after six months of treatment. [] Furthermore, no significant changes in glomerular filtration rate were observed, indicating that this compound did not adversely affect renal function in the study population. []

ANone: Currently, glucose-6-phosphate dehydrogenase (G6PD) deficiency status is the most crucial biomarker used before this compound administration. G6PD deficiency testing is mandatory because the drug can cause hemolysis in individuals with this condition. [, ]

ANone: this compound concentrations in biological samples like plasma are typically measured using sophisticated analytical techniques like high-performance liquid chromatography (HPLC) or liquid chromatography-mass spectrometry (LC-MS). [, ] These methods offer the sensitivity and specificity required to quantify this compound levels accurately.

ANone: Primaquine remains the mainstay drug for P. vivax radical cure and is the primary alternative to this compound. [, ] While both drugs belong to the 8-aminoquinoline class and effectively eliminate liver-stage hypnozoites, they differ significantly in their dosing regimens and potential for side effects.