Effects of Berberine on In Vivo Pharmacokinetics of Midazolam and Its Metabolite in Rats
10.3870/j.issn.1004-0781.2016.04.002
- VernacularTitle:盐酸小檗碱对大鼠体内咪达唑仑及其代谢产物药动学的影响
- Author:
Weiyu CHANG
;
Huawen XIN
;
Xia TANG
;
Meng OUYANG
;
Jianxun ZHONG
- Publication Type:Journal Article
- Keywords:
Berberine,hydrochloride;
Midazolam;
Cytochrome P450 enzyme 3A;
Pharmacokinetics;
Interactions,drug
- From:
Herald of Medicine
2016;35(4):331-336
- CountryChina
- Language:Chinese
-
Abstract:
Objective To examine the effect of berberine hydrochloride ( BER ) on the pharmacokinetic profiles of midazolam,a substrate of CYP3A,in rats. Methods The rats were intragastrically given different doses of BER (50,100, 200 mg?kg-1) or ketoconazole (75 mg?kg-1) for 10 days.Single-pass duodenum perfusion of 20 mg?kg-1 MDZ was performed and the inguinal artery was cannulated for blood sampling.Plasma concentrations of MDZ and 1'-OH-MDZ were analyzed by high performance liquid chromatography ( HPLC) with the CYP3A inhibitor ketoconazole serving as positive control. Results BER (50,100,200 mg?kg-1) and ketoconazole (75 mg?kg-1) could significantly increase the AUC(0-t),AUMC(0-t)and Cmax of MDZ in a dose-dependent manner ( P<0.05) ,and reduce the clearance rate ( CLz ) of MDA and its apparent volume of distribution in the body ( Vz ) ( P<0. 05). But they failed to dramatically affect the half-life ( t1/2z ) and the peak time ( tmax ) of MDZ. Additionally,BER ( 100,200 mg?kg-1 ) and ketoconazole ( 75 mg?kg-1 ) could significantly dose-dependently decrease the AUC(0-t),AUMC(0-t)and Cmaxof 1'-OH-MDZ,and profoundly increase the CLz,tmax and Vz of 1'-OH-MDZ (P<0.05),but they had no remarkable influences on the t1/2z.The ratio of AUC(1'-OH-MDZ)/AUC(MDZ) was decreased with the increase of BER concentration. Conclusion BER can inhibit the in vivo metabolism of MDZ in a dose-dependant manner, which is associated with the suppression of the activity of CYP3A.
