Mechanism-based Preclinical Approaches for the Evaluation of Drug-Drug Interactions.
Albert P. Li · Drug Metabolism and Pharmacokinetics · 2000
Pharmacokinetic drug-drug interactions (PDDI), in which the pharmacokinetic clearance of one drug is altered by a co-administered drug, can be divided mechanistically into two general categories: 1. inhibitory PDDI, the inhibition of the metabolic clearance of one drug by a co-administered drug; and 2. inductive PDDI, the enhancement of the metabolic clearance of one drug by a co-administered drug. It is believed that drug-drug interaction potential can be defined using a mechanism-based approach which includes the following sets of studies. 1: Identification of the major drug metabolizing enzymes. 2: Evaluation of the inhibitory potential for drug-metabolizing enzymes. 3. Evaluation of the induction potential for drug-metabolizing enzymes. Human liver-derived experimental systems: hepatocytes, liver microsomes, and cDNA-expressed microsomes, are useful experimental systems for this mechanistic approach to the evaluation of drug-drug interaction potential preclinical.