John Libbey Eurotext

Virologie

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Rôle de la pharmacogénétique dans le métabolisme et le transport des antirétroviraux Volume 15, issue 3, Mai 6

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Authors
McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote-Ste-Catherine Road, Montréal, Quebec, H3T 1E2, Canada, Indiana University School of medicine, Division of Clinical Pharmacology 1001 West 10 th Street, Wishard Hospital, Myers building, Indianapolis, IN, 46202 État-Unis, Centre de Recherche du Centre hospitalier de l’Université de Montréal (CRCHUM) Hôtel-Dieu, Centre de recherche, Pavillon Masson 3850, rue St-Urbain Montréal, Québec H2W 1T7, Canada, Université de Montréal, Faculté de pharmacie, C.P. 6128 Succursale Centre-Ville Montréal, Québec H3C 3J7, Canada

Wide intra- and inter-subject variability in antiretroviral drug response is observed. Pharmacotherapy of HIV-infected patients is challenging considering the great numbers of co-morbidities increasing the risk of drug-drug interactions. Drug-metabolism enzymes and drug-transporters regulate drug access to the systemic circulation, target cells and sanctuary sites; these factors determine pharmacokinetics and could explain variability in efficacy and adverse drug reactions associated with antiretroviral drugs. Notions related to the major enzymes (CYP450s and UGTs) involved in antiretroviral metabolism and drug-transporters are reviewed with an attention paid on genetic polymorphisms. Genetic polymorphisms affecting the activity or the expression of membrane proteins in the transport of drugs would be highlighted with examples such as neurotoxicity with efavirenz, nephrotoxicity with tenofovir, hepatotoxicity with nevirapine and hyperlibirubinemia associated with indinavir and atazanavir. The objective is to provide a better understanding on mechanisms involved in drug-disposition of antiretroviral helping out health care providers in the management of pharmacotherapy of HIV-infected patients.