Evaluation of a Bayesian hierarchical pharmacokinetic–pharmacodynamic model for predicting parasitological outcomes in Phase 2 studies of new antimalarial drugs

Abstract

The rise of multidrug-resistant malaria requires accelerated development of novel antimalarial drugs. Pharmacokinetic–pharmacodynamic (PK-PD) models relate blood antimalarial drug concentrations with the parasite–time profile to inform dosing regimens. We performed a simulation study to assess the utility of a Bayesian hierarchical mechanistic PK-PD model for predicting parasite–time profiles for a Phase 2 study of a new antimalarial drug, cipargamin. We simulated cipargamin concentration- and malaria parasite-profiles based on a Phase 2 study of eight volunteers who received cipargamin 7 days after inoculation with malaria parasites. The cipargamin profiles were generated from a two-compart..