Effect of sarpogrelate hydrochloride on cytochrome P450 2D1/2 in rats
10.3969/j.issn.1001-1978.2014.12.024
- VernacularTitle:盐酸沙格雷酯对大鼠体内细胞色素 P4502D1／2的影响
- Author:
Meijuan XU
;
Zhitao JIANG
;
Wenzhu ZHAO
;
Yuxin ZANG
;
Bingting SUN
;
Na RONG
;
Jiandong ZOU
;
Wenzheng JU
- Publication Type:Journal Article
- Keywords:
sarpogrelate hydrochloride;
dextromethor-phan;
cytochrome P4502D;
cytochrome P4502D6;
drug-drug interaction;
pharmacokinetics
- From:
Chinese Pharmacological Bulletin
2014;(12):1739-1742
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the influence of sarpog-relate hydrochloride (SH)on the pharmacokinetic pro-file of dextromethorphan (DM),the typical substrate of CYP2D1 /2,in rats when they were administered co-instantaneously.Methods A total of 1 2 SD rats were randomly divided into two groups:the control group (DM,1 0 mg·kg-1 )and the sarpogrelate group (SH, 1 0 mg·kg-1 ;DM,1 0 mg·kg-1 ),which received in-tragastric administration.Plasma samples were collected immediately before and at different time points after drug administration.A LC-MS /MS method was used to determine the concentrations of DM in rat plasma. Pharmacokinetic parameters were analyzed using Drug and Statistics (DAS 2.0).Results There were signif-icant differences in the pharmacokinetic parameters of DM,including T1 2 (2.49 h ±0.93 h vs 1 .47 h ±0.20 h,P <0.05 ),Cmax (325.7 μg·L -1 ±1 33.2 μg· L -1 vs 1 04.5μg·L -1 ±52.4 μg·L -1 ,P <0.05), AUC0 -t(785.5 μg·L -1 ·h ±451 .9 μg·L -1 ·h vs 244.8 μg·L -1 ·h ±1 68.3μg·L -1 ·h,P <0.05) and AUC0 -∞(804.7 μg·L -1 ·h ±445.6 μg·L -1 ·h vs 251 .4 μg·L -1 ·h ±1 73.4 μg·L -1 ·h,P<0.05 )between the two groups.Conclusion SH could significantly inhibit the elimination of DM,the substrate of CYP2D1 /2 in rats.
