Pharmacokinetic drug-drug interactions with methotrexate in oncology.
Fiche publication
Date publication
novembre 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Pr HERBRECHT Raoul
Tous les auteurs :
Leveque D, Santucci R, Gourieux B, Herbrecht R
Lien Pubmed
Résumé
Methotrexate is an antifolate agent used in the treatment of various cancers and some autoimmune diseases. In oncology, methotrexate is frequently administered at a high dose (>1 g/m(2)) and comes with various procedures to reduce the occurrence of toxicity and particularly to ensure optimal renal elimination. Drug-drug interactions involving methotrexate are the origin of severe side effects owing to delayed elimination of the antifolate and, more rarely, of decreased efficacy in relation to suboptimal exposure. Most of these interactions are driven by membrane drug transporters whose activity/expression can be inhibited by the interacting medication. In the last 10 years, research on drug transporters has permitted retrospective identification of the molecular mechanisms underlying drug-drug interactions with methotrexate. This article summarizes reported drug-drug interactions involving methotrexate in clinical oncology with reference to the role of drug transporters that control the disposition of the antifolate agent.
Référence
Expert Rev Clin Pharmacol. 2011 Nov;4(6):743-50.