Pharmacokinetic and Pharmacodynamic Profiles of Rapid-Acting Artemisinins in the Antimalarial Therapy

Qigui      Li; Peter   J.   Weina; Wilbur   K.   Milhous

Abstract

Artemisinin and its derivatives were discovered to be highly effective antimalarial drugs, which combine potent, rapid antimalarial activity with a wide therapeutic index and an absence of clinically important resistance. Artemisinins as a group are poorly efficacious at curing malaria as monotherapy. However, this shortfall is being overcome by using oral artemisinin-based combination therapy (ACT) and intravenous artesunate (AS) in sequential administration with slower acting antimalarial drugs. Pharmacokinetic and pharmacodynamic (PK/PD) evaluations demonstrate that the rapid efficacy of artemisinins is principally due to the drug peak concentration (Cmax), and other pharmacokinetic parameters, such as drug exposure level (AUC) and drug exposure time (half-life) tend to be of minor significance. The evaluation also demonstrated that AS is a superior in PK/PD achievements either following oral or intravenous administration when compared to other four artemisinin drugs. Most recently, a decrease in mortality (34.7%) has been demonstrated in a large study using intravenous AS, as opposed to the standard of care quinine injection. The fast efficacy and less mortality show that current artemisinins have great advantage over other antimalarials in ACTs for uncomplicated malaria and in sequential therapy of AS injection for severe and complicated malaria.

Keywords: Artemisinin, artesunate, dihydroartemisinin, arteether, artemether, artelinate, pharmacokinetics, pharmacodynamics, efficacy