Assessing the utility of an anti-malarial pharmacokinetic-pharmacodynamic model for aiding drug clinical development

Abstract

Background: Mechanistic within-host models relating blood anti-malarial drug concentrations with the parasite-time profile help in assessing dosing schedules and partner drugs for new anti-malarial treatments. A comprehensive simulation study to assess the utility of a stage-specific pharmacokinetic- pharmacodynamic (PK-PD) model for predicting within-host parasite response was performed. Methods. Three anti-malarial combination therapies were selected: artesunate-mefloquine, dihydroartemisinin-piperaquine, and artemether- lumefantrine. The PK-PD model included parameters to represent the concentration-time profiles of both drugs, the initial parasite burden and distribution across the paras..