The in vitro inhibition and induction of cytochrome P450 activities by bentysrepinine: a novel candidate of anti-hepatitis B virus drug
10.16438/j.0513-4870.2016-0523
- VernacularTitle:抗乙肝候选新药替芬泰对细胞色素P450酶的体外抑制和诱导作用研究
- Author:
Hui-rong FAN
1
;
Xiao-yan CI
2
;
Wei LI
2
;
Shi-qi DONG
3
;
Yong ZENG
2
;
Xiu-lin YI
2
;
Duan-yun SI
2
;
Chang-xiao LIU
2
Author Information
1. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China
2. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China
3. Tianjin University, Tianjin 300191, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
bentysrepinine;
cytochrome P450;
enzyme activity;
inhibition;
induction;
drug-drug interaction
- From:
Acta Pharmaceutica Sinica
2016;51(12):1864-
- CountryChina
- Language:Chinese
-
Abstract:
Bentysrepinine (Y101), a derivative of phenyalanine dipeptide, has a novel mechanism in the treatment of hepatitis B virus (HBV) infection with a good anti-HBV effect. In the present study, a fluorometric-based high throughput method using cytochrome P450 (CYP) screening kit was adopted to evaluate in vitro inhibition potential of Y101 on CYP isoenzymes by calculating remaining enzyme activities and inhibitory potential (IC50 values) using the determined values of fluorescence intensity. The result showed that Y101 exhibited little activity in the inhibition of CYP1A2, CYP3A4, CYP2C9, CYP2C19 and CYP2D6 (IC50 > 100 μmol·L-1). Y101 was used to treat human primary hepotocytes for 72 h, and the enzyme activities of CYP1A2, CYP2B6 and CYP3A4 were determined with a cocktail of probe substrates for the three CYP isoforms. The metabolites were simultaneously determined using a LC-MS/MS method. Y101 had no activity in the induction of CYP1A2, CYP2B6 and CYP3A4 on the basis of the following results:① The ratio of enzyme activities between test and control groups were all below than 1 (varied from 0.662 to 0.928); ② The induction potential of Y101 were lower than forty percent compared with that of positive groups. The above results suggest that Y101 has little activity in the regulation of metabolic drug-drug interactions based on the CYP isoform changes following co-administration of drugs.
