Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/56247
Type
ArticleCopyright
Restricted access
Embargo date
2099-12-30
Collections
Metadata
Show full item record
AN UPDATE ON PHARMACOGENETIC FACTORS INFLUENCING THE METABOLISM AND TOXICITY OF ARTEMISININ-BASED COMBINATION THERAPY IN THE TREATMENT OF MALÁRIA
ACT
CYP
Malaria
adverse events
antimalarial drug
metabolism
pharmacogenetics
Author
Affilliation
Department of Microbiology. Tumor and Cell biology, Karolinska Institutet. Solna, Sweden/Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute. University of Lisbon. Lisbon, 1749-016, Portugal.
Department of Epidemiology of Parasitic Diseases. Faculty of Pharmacy. Malaria Research and Training Center. University of Science, Techniques and Technologies of Bamako. Bamako, Mali.
Molecular Biology and Malaria Immunology Research Group. René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brasil.
Department of Microbiology. Tumor and Cell biology, Karolinska Institutet. Solna, Sweden.
Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute. University of Lisbon. Lisbon, 1749-016, Portugal/Department of Parasitology.Institute of Biomedical Sciences. University of São Paulo., São Paulo,SP, Brazil.
Department of Microbiology. Tumor and Cell biology, Karolinska Institutet. Solna, Sweden/Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute. University of Lisbon. Lisbon, 1749-016, Portugal/ Global Health and Tropical Medicine. Institute of Hygiene and Tropical Medicine. Nova University of Lisbon, Portugal.
Department of Epidemiology of Parasitic Diseases. Faculty of Pharmacy. Malaria Research and Training Center. University of Science, Techniques and Technologies of Bamako. Bamako, Mali.
Molecular Biology and Malaria Immunology Research Group. René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brasil.
Department of Microbiology. Tumor and Cell biology, Karolinska Institutet. Solna, Sweden.
Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute. University of Lisbon. Lisbon, 1749-016, Portugal/Department of Parasitology.Institute of Biomedical Sciences. University of São Paulo., São Paulo,SP, Brazil.
Department of Microbiology. Tumor and Cell biology, Karolinska Institutet. Solna, Sweden/Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute. University of Lisbon. Lisbon, 1749-016, Portugal/ Global Health and Tropical Medicine. Institute of Hygiene and Tropical Medicine. Nova University of Lisbon, Portugal.
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.
Keywords
ABC transporterACT
CYP
Malaria
adverse events
antimalarial drug
metabolism
pharmacogenetics
Share