Scientific and regulatory perspectives on metabolizing enzyme-transporter interplay and its role in drug interactions: challenges in predicting drug interactions.
Both metabolizing enzymes and drug transporters play important roles in modulating drug absorption, distribution, metabolism and elimination. Acting alone or in concert with each other they can affect the pharmacokinetics and pharmacodynamics of a drug. This paper will present cases from recent reviews of new drug application (NDA) and literature that exemplify the role of metabolizing enzyme-transporter interplay in a drug's disposition, and discuss challenges in predicting drug interactions. Finally, the discussion will focus on the need to leverage current knowledge to obtain more meaningful drug interaction information.
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland 20993, USA. leik.zhang@fda.hhs.gov
Lei
L
Zhang
Yuanchao
Y
Zhang
Shiew-Mei
SM
Huang
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D004347:Drug Interactions; D004798:Enzymes / Q000378:metabolism*; D006801:Humans; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D004798:Enzymes; D004364:Pharmaceutical Preparations