Novel 3,3'-disubstituted-5,5'-bi(1,2,4-triazine) compounds with potent in vitro activity against Plasmodium falciparum parasites were recently discovered. To improve the pharmacokinetic properties of the triazine derivatives, a new structure-activity relationship (SAR) investigation was initiated with a focus on enhancing the metabolic stability of lead compounds.
Chloroquine is the first-line therapy against the asexual stages of Plasmodium vivax . There is a high variation of chloroquine plasma levels after therapeutic doses, which can lead to inadequate exposure to the drug. The gender influence was low regarding the disposition of the drug, which is relevant as there are significant physiological variations between male and female patients.
Garcinia mangostana L. (mangosteen) is a famous tropical fruit that contains a large number of xanthones. Regular consumption of mangosteen may confer health benefits and prevent some diseases, such as malaria. Quinone reductase 2 (QR-2) is a cytosolic enzyme found in human red blood cells, and it is becoming a target for chemoprevention because it is involved in the mechanisms of several diseases, including malaria.
(+)-SJ000557733 (SJ733) is a novel, orally bioavailable inhibitor of Plasmodium falciparum ATP4. In this first-in-human and induced blood-stage malaria phase 1a/b trial, we investigated the safety, tolerability, pharmacokinetics, and antimalarial activity of SJ733 in humans.
KAF156 is a novel antimalarial drug that is active against both liver- and blood- stage Plasmodium parasites, including drug-resistant strains. Here, we investigated the causal prophylactic efficacy of KAF156 in a controlled human malaria infection (CHMI) model.
Chloroquine has been used for the treatment of malaria for more than 70 years; however, chloroquine pharmacokinetic (PK) and pharmacodynamic (PD) profile in Plasmodium vivax malaria is poorly understood. The objective of this study was to describe the PKPD relationship of chloroquine and its major metabolite, desethylchloroquine, in a P. vivax volunteer infection study.
Mass administration of antimalarial drugs and ivermectin are being considered as potential accelerators of malaria elimination. The safety, tolerability, pharmacokinetics, and mosquito‐lethal effects of combinations of ivermectin, dihydroartemisinin‐piperaquine, and primaquine were evaluated. Coadministration of ivermectin and dihydroartemisinin‐piperaquine resulted in increased ivermectin concentrations with corresponding increases in mosquito‐lethal effect across all subjects.
MMV390048 is the first Plasmodium phosphatidylinositol 4-kinase inhibitor to reach clinical development as a new antimalarial. We aimed to characterize the safety, pharmacokinetics and antimalarial activity of a tablet formulation of MMV390048.
MMV390048 is a novel antimalarial compound that inhibits Plasmodium phosphatidylinositol-4-kinase. The safety, tolerability, pharmacokinetic profile, and antimalarial activity of MMV390048 were determined in healthy volunteers in three separate studies. A first-in-human, double-blind, randomized, placebo-controlled, single-ascending-dose study was performed. Additionally, a volunteer infection study investigated the antimalarial activity of MMV390048 using the Plasmodium falciparum induced blood-stage malaria (IBSM) model.
There is an increased recognition of the need to identify and quantify the impact of genetic polymorphisms on drug-drug interactions. This study investigated the pharmacogenetics of the pharmacokinetic drug-drug interaction between nevirapine and artemether-lumefantrine in HIV-positive and HIV-negative adult Nigerian subjects. Thirty each of HIV-infected patients on nevirapine-based antiretroviral therapy and HIV-negative volunteers without clinical malaria, but with predetermined CYP2B6 c.516GG and TT genotypes, were administered a complete treatment dose of 3 days of artemether-lumefantrine. Rich pharmacokinetic sampling prior to and following the last dose was conducted, and the plasma concentrations of artemether/dihydroartemisinin and lumefantrine/desbutyl-lumefantrine were quantified using tandem mass spectrometry.