An improved pharmacometric model for artesunate treatment of falciparum malaria

Abstract

Previous mathematical models characterising the pharmacokinetic and pharmacodynamic properties of artemisinins in-vivo have not accounted satisfactorily for observed dose-response relationships. We present a new mathematical model of antimalarial pharmacodynamics which incorporates the hypothesis that parasites enter a transitional unresponsive state after contact with artemisinins, followed either by delayed death or reactivation. The model predictions are consistent with both in vitro and in vivo study results.