Translational Pharmacokinetic and Pharmacodynamic Evaluation of Mefloquine Against Plasmodium falciparum Using a Hollow Fiber Infection Model

The HFIM exposure profile maintained clinically relevant peak concentrations with the long clinical PK half-life of mefloquine. Under these dynamic exposure conditions, mefloquine produced sustained suppression of parasitemia across successive life cycles relative to both control conditions, consistent with concentration-driven blood-stage activity. The estimated IC50 was 0.03 mg/L. Together, this study demonstrated that the commonly used plastic-based HFIM can simulate clinically relevant PK profiles and characterize the antimalarial PD against blood-stage <i>P. falciparum</i>.

This addresses limitations of static in vitro assays and reduces the reliance on animal models, where preclinical-to-clinical concordance can be poor. Thereby, HFIM provides a promising framework for optimizing antimalarial dosing strategies. Future studies will extend this approach to rational evaluation of combination therapies using PK/PD-guided regimen design to improve clinical relevance.