The drug-drug interaction mediated by efflux transporters and CYP450 enzymes.
- Author:
Chong WANG
;
Ke-Xin LIU
- Publication Type:Journal Article
- MeSH:
ATP Binding Cassette Transporter, Sub-Family G, Member 2;
ATP-Binding Cassette Transporters;
metabolism;
ATP-Binding Cassette, Sub-Family B, Member 1;
metabolism;
Biological Availability;
Cytochrome P-450 CYP3A;
metabolism;
Cytochrome P-450 Enzyme System;
metabolism;
Drug Interactions;
Humans;
Multidrug Resistance-Associated Proteins;
metabolism;
Neoplasm Proteins;
metabolism;
Substrate Specificity
- From:
Acta Pharmaceutica Sinica
2014;49(5):590-595
- CountryChina
- Language:Chinese
-
Abstract:
Multidrug regimens and corresponding drug interactions cause many adverse reactions and treatment failures. Drug efflux transporters: P-glycoprotein (P-gp), multidrug resistance associated protein (MRP) and breast cancer resistance protein (BCRP) in conjunction with metabolizing enzymes (cytochrome P450, CYP450) are major factors in such interaction. In recent years, a large number of studies have shown that P-gp plays a role in the oxidative metabolism of its substrates that are also substrates of CYP3A4. Combined actions of P-gp and CYP3A could account in some part for the low oral bioavailability determined for many of these dual substrates. P-gp along with efflux transporters (MRP and BCRP) having overlapping substrate specificity plays critical role in drug disposition. The relationship between MRP or BCRP and CYP3A is similar to that between P-gp and CYP3A. In this paper, we summarize the classification of efflux transporters, the main metabolizing enzymes CYP3A, clinical significance interactions mediated by efflux transporters and CYP450 enzymes and in vitro studies.
