US EPA

6806726 

Journal Article 

Review 

Drug-drug Interactions of Angiotensin Converting Enzyme Inhibitors Mediated by Metabolizing Enzymes and Transporters 

Sun, P; Liu, K 

2018 

Yes 

Current Drug Metabolism
ISSN: 1389-2002
EISSN: 1875-5453 

Bentham Science Publishers B.V. 

19 

13 

1119-1129 

English 

30062958 

10.2174/1389200219666180730163953 

WOS:000482655100001 

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.

METHOD: 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, 2017), 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. 

Angiotensin converting enzyme inhibitors; Drug-drug interactions; Hypertension; Metabolizing enzymes; Pharmacokinetic; Transporters; 2,4 dinitrophenol; angiotensin; calcium ion; captopril; carboxylesterase; cefroxadine; cytochrome P450; dipeptidyl carboxypeptidase inhibitor; diuretic agent; drug metabolizing enzyme; enalapril; enalaprilat; fosinopril; gemcabene; glucose; glucose transporter 1; indican; levofloxacin; methotrexate; microcystin LR; peptide transporter 1; peptide transporter 2; polycyclic aromatic hydrocarbon; quinapril; ramipril; sitagliptin; streptozocin; temocaprilat; urate; vasodilator agent; carrier protein; dipeptidyl carboxypeptidase inhibitor; adrenergic activity; bioavailability; blood brain barrier; drug interaction; electrochemistry; gene overexpression; human; liver cell; pharmacokinetics; protein expression; Review; transport assay; Trypanosoma cruzi; animal; drug interaction; metabolism; Angiotensin-Converting Enzyme Inhibitors; Animals; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Membrane Transport Proteins