Drug-drug interactions of angiotensin converting enzyme inhibitors mediated by metabolizing enzymes and transporters.

BACKGROUND: Patients with hypertension usually have to be treated with angiotensin converting enzyme (ACE) inhibitors, and are therefore more exposed to drug-drug interactions (DDIs) by various mechanisms, especially the mechanisms based on drug metabolizing enzymes and transporters.

OBJECTIVE: This review article focuses on the pharmacokinetic interaction mechanisms with ACE inhibitors based on drug metabolizing enzymes and transporters, and the identification of these underlying mechanisms would help physicians and patients to predict, detect and prevent DDIs.

METHODS: To identify the pharmacokinetic interaction mechanisms based on drug metabolizing enzymes and transporters of ACE inhibitors. An electronic search of PubMed, Medline, Science Direct, and Springer-Link database was conducted (from 1950 to December, 2016), using drug interactions, cytochrome P450, carboxylesterase, names of transporters, names of ACE inhibitors and pharmacokinetics as keywords.

RESULTS AND CONCLUSION: Inhibition of metabolizing enzymes and transporter system can markedly alter the concentrations of ACE inhibitors. The genetic polymorphisms in the enzymes in some of the specific isoforms seem to explain the inter-individual differences in ACE inhibitors metabolism, and also the inter-individual variation in the pharmacokinetics of ACE inhibitors may be caused by changes in transporter function. Understanding the knowledge of how ACE inhibitors are metabolized and transported is important in predicting and managing DDIs. The data on the roles of drug metabolizing enzymes and transporters in the DDIs of ACE inhibitors should be studied and the selection of ACE inhibitors should be individualized to prevent DDIs in clinic.