An update on pharmacogenetic factors influencing the metabolism and toxicity of artemisinin-based combination therapy in the treatment of malaria

Abstract

Introduction: Artemisinin-based combination therapies (ACTs) are recommended first-line antimalarials for uncomplicated Plasmodium falciparum malaria. Pharmacokinetic/pharmacodynamic variation associated with ACT drugs and their effect is documented. It is accepted to an extent that inter-individual variation is genetically driven, and should be explored for optimized antimalarial use. Areas covered: We provide an update on the pharmacogenetics of ACT antimalarial disposition. Beyond presently used antimalarials, we also refer to information available for the most notable next-generation drugs under development. The bibliographic approach was based on multiple Boolean searches on PubMed covering all recent publications since our previous review. Expert opinion: The last 10 years have witnessed an increase in our knowledge of ACT pharmacogenetics, including the first clear examples of its contribution as an exacerbating factor for drug–drug interactions. This knowledge gap is still large and is likely to widen as a new wave of antimalarial drug is looming, with few studies addressing their pharmacogenetics. Clinically useful pharmacogenetic markers are still not available, in particular, from an individual precision medicine perspective. A better understanding of the genetic makeup of target populations can be valuable for aiding decisions on mass drug administration implementation concerning region-specific antimalarial drug and dosage options.