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

Aims Artesunate and artemether are the two most widely used artemisinin der ivatives in the treatment of uncomplicated Plasmodium falciparum malaria, b ut there is little information on their comparative pharmacokinetics. The a im of this study was to examine the relative oral antimalarial bioavailabil ity 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 pati ents in western Thailand with acute uncomplicated Plasmodium falciparum mal aria. Antimalarial activity was compared using a previously validated, sens itive bioassay. Results Despite a 29% lower molar dose, oral artesunate administration resu lted in significantly larger mean area under the plasma antimalarial activi ty time Curve and median maximum plasma antimalarial activity than after or al artemether (P less than or equal to0.02). The mean (95% CI) oral antimal arial bioavailability of artemether, relative to oral artesunate, corrected for molar dose was 58 (40-76)%. The mean (95% CI) relative antimalarial bi oavailability of artemether,vas lower oil the first day of treatment, 31 (1 7-100)%, compared to the second day, 72 (44-118)%. (P = 0.018). In vivo par asite clearance and time above the in vitro IC90 were similar for the two d rugs, despite considerable differences in C-max and AUC. Conclusions The oral antimalarial bioavailability following artemether was significantly lower than that after artesunate. Artemether oral antimalaria l bioavailability is reduced in acute malaria.