A comparison of oral artesunate and artemether antimalarial bioactivities in acute falciparum malaria

Aims Artesunate and artemether are the two most widely used artemisinin derivatives in the treatment of uncomplicated Plasmodium falciparum malaria, but there is little information on their comparative pharmacokinetics. The aim of this study was to examine the relative oral antimalarial bioavailability and pharmacokinetics of the two derivatives. Methods The pharmacokinetic properties of oral artesunate and artemether (4 mg kg −1 ) were compared in a randomized cross‐over study of 14 adult patients in western Thailand with acute uncomplicated Plasmodium falciparum malaria. Antimalarial activity was compared using a previously validated, sensitive bioassay. Results Despite a 29% lower molar dose, oral artesunate administration resulted in significantly larger mean area under the plasma antimalarial activity time curve and median maximum plasma antimalarial activity than after oral artemether ( P ≤ 0.02). The mean (95% CI) oral antimalarial bioavailability of artemether, relative to oral artesunate, corrected for molar dose was 58 (40–76)%. The mean (95% CI) relative antimalarial bioavailability of artemether was lower on the first day of treatment, 31 (17–100)%, compared to the second day, 72 (44–118)% ( P = 0.018). In vivo parasite clearance and time above the in vitro I C 90 were similar for the two drugs, despite considerable differences in C max and AUC. Conclusions The oral antimalarial bioavailability following artemether was significantly lower than that after artesunate. Artemether oral antimalarial bioavailability is reduced in acute malaria.