Pharmacokinetics and Pharmacodynamics of Antimalarial Drugs

Abstract

Malaria remains a major cause of morbidity and mortality worldwide, particularly in tropical and subtropical regions, despite considerable progress in prevention and treatment. The increasing prevalence of antimalarial drug resistance and variability in drug response among different patient populations continue to challenge effective disease management. Pharmacokinetic (PK) and pharmacodynamic (PD) principles are fundamental to understanding drug disposition, optimizing dosage regimens, improving therapeutic efficacy, and minimizing toxicity and resistance. This review provides a comprehensive overview of the PK/PD characteristics of established and emerging antimalarial agents and discusses their role in optimizing malaria treatment. Recent advances in population pharmacokinetic and physiologically based pharmacokinetic modeling, pharmacometric approaches, exposure response analysis, and model informed drug development have enhanced dose optimization and supported individualized therapy. The review also highlights PK/PD considerations in special populations, including children, pregnant women, older adults, and patients with hepatic or renal impairment. Furthermore, emerging strategies such as pharmacogenomics, therapeutic drug monitoring, artificial intelligence, machine learning, long acting antimalarial formulations, and triple artemisinin based combination therapies are discussed for their potential to improve treatment outcomes and address drug resistance. The integration of these innovative approaches with molecular resistance surveillance and precision medicine is expected to enhance clinical decision making, accelerate the development of next generation antimalarial therapies, and contribute to sustainable malaria control and global elimination efforts.