Population pharmacokinetics of artesunate and its active metabolite dihydroartemisinin

摘要: Artemisinin compounds are the most potent anti-malarial drugs available in market. Today, malaria treatment is largely relies on artemisinin-based combination therapies. Artesunate (AS) widely used artemisinin derivative. In this thesis, we characterized population pharmacokinetics of AS and its active metabolite dihydroartemisinin (DHA) following oral administration different populations. Chapter II, developed a pharmacokinetic model DHA healthy subjects. These subjects received either singleor multipledosing AS, as monotherapy regimen or with pyronaridine, without food. III, adult pediatric patients uncomplicated falciparum vivax who were administered pyronaridine/artesunate once daily for 3 days. We modeled data simultaneously using parent-metabolite that assumed complete conversion to DHA. Following administration, rapidly absorbed maximum concentrations reached at about 0.5 hours postdose. converted then undergoes rapid metabolism, an elimination half-life 0.8 malarial patients. Inter-individual variability almost all parameters residual both estimated by models. Substantial was seen between subjects, intake food dose found delay absorption significantly, but not extent absorption. Weight also included determinant clearance. When modeling from patients, weight part priori established allometric function. No other covariates examined analysis statistically significant.