合用盐酸小檗碱对环孢素A人体药动学的影响

Effect of berberine HCl on pharmacokinetics of cyclosporine A in human

目的:研究合用盐酸小檗碱(Ber)对肾移植受者和健康受试者环孢素A(CsA)药动学的影响,以分析两药相互作用发生的部位。方法:采用自身对照的方法,12例健康受试者和6例肾移植术后1个月的患者在个体CsA剂量不变的前提下,改变给药途径、两药同时或分开服用和改变合用频率等条件,按时间点采集血样,用FPIA法测定全血CsA浓度,并计算出药动学参数。结果:肾移植受者合用Ber和CsA后,CsA的AUC平均增加(34.5±17.8)%;口服6mg·kg-1CsA和Bet 0.3g,bid,末次两药分开服用的健康受试者平均AUC没有增加;口服3mg·kg-1CsA和Ber 0.3g,bid,末次两药同时服用的健康受试者平均AUC增加(19.2±10.4)%;静注3mg·kg-1CsA和口服Ber 0.3g,bid的健康受试者平均AUC减少(16.0±7.2)%。结论:两药必须同时服用方可发生相互作用,只有两药均在肠道时,CsA的吸收才会增加,提示肠道可能是Ber影响CsA吸收的作用部位之一,Ber可能增加CsA的吸收或减少肠代谢。Ber与CsA同时口服可增加CsA的生物利用度。

Objective:To study the effect of berberine HCl on pharmacokinetics of cyclosporine A (CsA) in healthy volunteers and recipients of renal transplantation. Methods:12 healthy volunteers and 6 patients after one month of renal transplantation were involved in the self-control study. A con-stant dose of CsA was given to them all, and berberine HCl was given simultaneously or separately, and the frequency of co-administration was alternated. Blood samples were taken according to time sched-ule.The CsA level in blood samples were measured by FPIA (fluorescence polarization immunoassay) and the pharmacokinetic parameters were calculated. Results: The mean AUC value for CsA in patients receiving co-administration of CsA and berberine HCl was increased by (34. 5±17. 8)% and didn't increase in healthy volunteers receiving twice daily co-administration dose of oral 6mg·kg-1 CsA and 0. 3g berberine HCl with a last separated dose of CsA and berberine HCl. The mean AUC value for CsA in healthy volunteers receiving twice daily separated dose of oral 3mg·kg-1 CsA and 0. 3g berberine HCl with a last co-administration dose of CsA and berberine HCl was increased by (19. 2±10. 4) % and the mean AUC value for CsA in healthy volunteers receiving twice daily iv injection of 3mg·kg-1 CsA and oral 0. 3mg berberine HCl was decreased by (16. 0±7. 2)%. Conclusion: Drug interactions between CsA and berberine HCl occurred only in co-administration and the increase in absorption of CsA occurred only when the two drugs were met in intestinal tract.