摘要
目的:探讨盐酸黄连素(berberine hydrochloride,BBR)是否影响P糖蛋白(P-glycolprotein,P-gp)底物罗丹明123(rhodamine 123,Rh 123)在大鼠体内的代谢。方法:以生理盐水作为阴性对照,以P-gp抑制药维拉帕米为阳性对照。不同组别大鼠分别给予不同剂量BBR或维拉帕米(4 mg·kg-1)连续灌胃10 d后,单次灌胃Rh123(5 mg·kg-1),自尾静脉采血,HPLC法测定大鼠血浆中Rh123的浓度,研究Rh123在大鼠体内的代谢。结果:建立的大鼠血浆中Rh123的HPLC检测方法完全符合Rh123大鼠血浆样本分析测试的要求,具有较高的灵敏度和特异性。大鼠给予不同药物后各组Rh 123的主要药动学参数:AUC(0-t)(μg·h·L-1)分别为:阴性对照组(48.36±6.4)、BBR 50 mg·kg-1组(59.58±13.37)、BBR 100 mg·kg-1组(77.51±6.84)、BBR 200 mg·kg-1组(95.49±15.99)、维拉帕米4 mg·kg-1组(93.01±13.07);Cmax(μg·L-1)分别为:阴性对照组(4.41±0.45)、BBR 50 mg·kg-1组(10.18±5.59)、BBR 100 mg·kg-1组(11.78±3.19)、BBR 200 mg·kg-1组(16.25±8.65)、维拉帕米4 mg·kg-1组(11.39±2.76)。BBR 100,200 mg·kg-1和维拉帕米4 mg·kg-1均能够显著升高Rh 123的AUC(0-t)(P<0.01);BBR 50,100,200 mg·kg-1和维拉帕米4 mg·kg-1均能够显著升高Rh 123的Cmax(P<0.05)且呈剂量依赖性。结论:黄连素可以显著抑制Rh123的代谢,该抑制作用很有可能与BBR抑制了P-gp的活性有关。
Objective： To evaluate the effect of berberine hydrochloride （BBR） on the pharmacokinetic profiles of a substrate of P- glycolprotein（P-gp） rhodamine 123 （Rh123） in male rats. Methods： The rats were given BBR with various dosages or 4 mg · kg-1 verapamil for 10 days by intragastric administration. The blood was obtained from the caudal vein of rats after intragastric administration of single dose of 5 mg · kg-1 Rh123. HPLC was used to analyze the plasma concentration of Rh123, and then the metabolism of Rh123 was studied. The physiological saline group was used as the negative control and verapamil group was the positive control. Results： The established HPLC detection method of Rh123 in rats with high sensitivity and specificity was developed to meet the requirements of plasma sample analysis. The pharmacokinetic parameters of Rh123 after the co-administration with BBR were as follows： AUC〈0-1） （ μg ·h ·L-1） was （48.36 ±6.4） for the negative control, （59.58 ± 13.37）,（77.51 ±6.84） and （95.49 ± 15.99）for BBR with the dosage of 50, 100 and 200 mg · kg - 1, respectively, and （93.01 ± 13.07 ） for 4 mg · kg - 1 verapamil; C± （ μg · L - 1 ） was （ 4.41 ± 0.45）for the negative control, and （10.18 ±5.59）, （11.78 ±3.19） and （16.25 ±8.65）for BBR with the dosage of 50, 100 and 200 mg · kg - 1, respectively, and （ 11.39 ± 2.76） for 4 mg · kg- 1 verapami]. BBR with the dosage of 100 and 200 mg· kg- 1 and ver- apamil with the dosage of 4 mg · kg - 1 could significantly increase AUC（0-1） of Rh123 （ P 〈 0.01 ）, and BBR with the three dosages and 4 mg · kg-1 verapamil could increase Cm± of Rh123（ P 〈 0.05 ）. Conclusion： BBR can significantly inhibit the metabolism of Rh123 （a probe drug of P-gp）, which has close relationship with the inhibition effect of berberine on P-gp transporter.
出处
《中国药师》
CAS
2014年第8期1281-1285,共5页
China Pharmacist
