Contribution of genetic polymorphisms of the CYP3A4, CYP3A5 and MDR1 genes to cyclosporine disposition
- VernacularTitle:CYP3A4,CYP3A5和MDR1基因多态性对环孢素处置的影响
- Author:
Yongfang HU
;
Honghao ZHOU
- Publication Type:Journal Article
- Keywords:
cyclosporine;
CYP3A4;
CYP3A5;
MDR1;
disposition
- From:
Chinese Pharmacological Bulletin
1987;0(03):-
- CountryChina
- Language:Chinese
-
Abstract:
Cyclosporine is an immunosuppressive drug largely used in organ transplantation.It is characterized by a narrow therapeutic index and wide interindividual variability in its pharmacokinetics. Cyclosporine is metabolized primarily by CYP3A4 and CYP3A5 in the liver and small intestine and also substrate for P-gp, encoded by MDR1. The interindividual heterogeneity in enzymatic activity of small intestine and liver CYP3A4 and CYP3A5, and intestine P-gp have contributed to oral cyclosporine pharmacokinetics in kidney, heart,liver and lung transplant patients. The differences in enzymatic activity of CYP3A and P-gp are believed to be due to CYP3A4, CYP3A5 and MDR1 genetic mutation. Therefore, a investigation which the effect of sequence variants in gene encoding drug-metabolizing enzymes and drug transporter to cyclosporine disposition may lead to individualized drug dosing and improved therapeutics.
