五酯胶囊与他克莫司的相互作用研究

Interaction of Wuzhi Capsule and Tacrolimus

关键词:  五酯胶囊  他克莫司  药动学

Key words:  Wuzhi Capsule  tacrolimus  pharmacokinetics  herb-drug interaction  Healthy volunteers  HPLC  LC-MS/MS

摘要:

摘要：目的 通过研究五酯胶囊(Wuzhi Capsule，WZC)与他克莫司(tacrolimus，TAC)在健康人体内的相互作用，初步探讨两药合用的剂量比，为WZC成为TAC节约剂及临床合理使用两药提供理论依据。方法 8名健康志愿者口服给药2 mg TAC，研究单次给药WZC后对体内TAC血药浓度的影响；将40名健康志愿者随机分为5组，口服给药2 mg TAC 5 min后，分别给予0，1，2，6，7粒WZC，于给药前、不同时间点静脉采血，置于抗凝管中，分析测定。结果 本方法测得合用不同剂量五脂胶囊后TAC体内主要药动学参数，T_max=(3.125±1.356)h，C_max=(43.539±10.656)ng·mL^-1， AUC_0→t=(459.3±114.2)ng·h·mL^-1，C_{12 h}与C_{24 h}维持在5~10 ng·mL^-1，CL/F从51.67%降至27%。结论 WZC能够使血液中TAC的浓度显著升高，并且WZC还可以同时降低TAC维持有效血药浓度的剂量，从而大大缩小器官移植患者TAC的使用剂量，达到缩减移植患者医疗费用的经济效益。 关键词：五酯胶囊；他克莫司；药动学

Abstract:

ABSTRACT: OBJECTIVE To access the ratio of WAC and TAC in the combination therapy by evaluating the interaction between the two drugs in healthy volunteers in order to provide the basis for clinical rational drug combination therapy. METHODS The influence of single dose WZC on the TAC blood concentration will be evaluated on 8 healthy volunteers. They will be given WZC after being orally administrated TAC, and the blood concentration of TAC will be evaluated. Then the influence of multiple doses of WZC on TAC blood concentration will be studied on 40 healthy volunteers, which were divided into 5 groups randomly. Different doses of WZC will be administrated 5 min later than the TAC. and the blood concentration of TAC will be evaluated before and at different time points after the WZC administration. RESULTS The pharmacokinetic parameters of TAC in healthy volunteers after co-administrated different doses of WZC were obtained, T_max=(3.125±1.356)h, C_max=(43.539±10.656)ng·mL^-1, AUC_0→t=(459.3±114.2)ng·h·mL^-1, C_{12 h} or C_{24 h} was maintained at 5~10 ng·mL^-1, CL/F ration has fallen from 51.67% to 27%. CONCLUSION The blood concentration of TAC increased when being co-administrated with WZC. The TAC dose for the organ transplant patient could also be decreased when WZC were used together. Therefore, by combined with WZC, the economic benefit could be achieved via reducing the medical expenses of TAC for the organ transplant patient.