Effects of Four Dihydropyridine Calcium Antagonists on CYP3 A4 Enzyme Activity Induced By Dexametha-sone in Female Rats
- VernacularTitle:4种二氢吡啶类钙拮抗药对地塞米松诱导雌性大鼠 CYP3 A4酶活性的影响
- Author:
Junan SUN
;
Xuecheng HAN
;
Zongling XIA
;
- Publication Type:Journal Article
- Keywords:
Dihydropyridine calcium antagonist;
CYP3A4;
Drug interaction
- From:
China Pharmacist
2014;(12):2007-2010
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the inhibition effects of four dihydropyridine calcium antagonists felodipine, nicardipine, lercani-dipine and nifedipine on CYP3A4 enzyme to provide the theoretical basis for the understanding of the drug interactions between dihydro-pyridine calcium antagonists and other drugs. Methods:Using the probe drugs method, the SD female rats induced by 80 mg·kg-1 · d-1 dexamethasone for three days were divided into the negative control group, positive control group, four DHPs groups with six ones in each. Dapsone was used as the probe substrate, and the concentration was determined by HPLC. Data analysis software WinNonLin was used in the pharmacokinetic model fitting process and the paired t-test was used in the statistical analysis. Results: AUC0-24 and CL/F of dapsone in the negative control group showed statistically significant differences when compared with those in the four DHPs groups and the positive group (P<0. 05). Although the inhibition effect of the four DHPs was in the order of nifedipine inhibition >nicardipine > lercanidipine > felodipine, the difference was not statistically significant (P>0. 05). Cmax of dapsone in the DHPs groups and the positive group had no statistically significant difference when compared with that in the negative control group ( P>0. 05). Conclusion:Although there are different inhibition effects on CYP3A4 among the four DHPs, the differences are not significant in vivo, and there is no influence on the combination drugs which is not mainly metabolized by CYP3A4.
