五酯胶囊对健康受试者他克莫司药动学的影响

Evaluation of drug interaction of tacrolimus with Wuzhi capsules

目的:研究健康受试者合用中药制剂五酯胶囊(Wuzhi-capsule,WZ)前后他克莫司(tacrolimus,Tac)的动力学过程,观察两药是否存在相互作用。方法:研究分两期,12例健康男性志愿者在第一周期单剂口服Tac 2 mg后,开始连续服用五酯胶囊3粒,bid,连服13 d;在第二周期再单剂口服Tac 2 mg,同时服用五酯胶囊3粒。每期口服Tac后即按设计的时间采血,用ELISA法测定全血Tac浓度,并计算药动学参数。结果:合用五酯胶囊前后Tac的主要药动学参数:AUC0~24 h分别为(129.48±68.90)和(274.82±64.93)μg.L-1.h;t1/2分别为(9.39±3.13)和(8.11±3.56)h;CL(s)分别为(17.72±17.30)和(6.55±1.55)L.h-1;Tmax分别为(1.42±0.36)和(1.83±0.25)h;Cmax分别为(22.21±10.61)和(66.44±21.27)μg.L-1;V/F(C)分别为(179.94±41.27)和(72.81±28.07)L。与合用五酯胶囊前相比,Tac的AUC0~24 h和Cmax分别增加164.2%和227.1%,CL(s)降低49.0%,Tmax显著延迟。结论:五酯胶囊能显著增加Tac的血浓度和生物利用度。

Objective： To assess the drug interaction of WuZhi capsulea with tacrolimus. Meth- ods： 12 healthy male volunteers were orally administered with a single dose of tacrolimus 2 mg, and sub- sequently with WuZhi capsules （3 capsules each） , twice daily for 13 days. After the wash-out period, these volunteers were orally administered with an additional single dose of tacrolimus 2 mg combined with 3 Wuzhi capsules. The blood samples were collected from the volunteers at certain timepoints after each cycle of the administration to measure pharmacokinetic profile of tacrolimus by enzyme-linked immunosor- bent assay. The pharmacokinetic parameters of tacrolimus were calculated by noncompartmental tech- niques. Results： The pharmacokinetic parameters of tacrolimus pre- and post-coadministration with WuZhi capsules were as follows： AUC0_24h （ 129.48 _＋ 68.90） vs. （274.82 ＋ 64.93 ）/xg ~ L-j ~ h; t,/2（9.39_＋3.13） vs. （8.11 _＋3.56）h; CL（s） （17.72_＋17.30） vs. （6.55 _＋ 1.55）L＇h-＇;T~,x （1.42_＋0.36） vs. （1.83_＋0.25）h; C^ax（22.21_＋10.61） vs. （66.44_＋21.27）/xg-L-J; V/F（C） （179.94 _＋41.27） vs. （72.81 _＋ 28.07） L. Compared to pre-coadministration of WuZhi capsules, the patients had an average increment of AUC and C~,~ of tacrolimus of 164.2% and 227.1% , respectively, an average decrement of CL/F of 49.0% , and a significantly delaying of Tin,x. Conclusion： WuZhi cap- sules significantly increase the blood concentration and oral bioavailability of tacrolimus.