透骨消痛胶囊单次与多次给药对大鼠体内药代动力学行为的影响

目的:开展透骨消痛胶囊单次和多次给药后大鼠体内药代动力学研究,探讨不同给药方式时血药浓度与药动学相关参数的关联性,为中药复方的临床合理用药提供参考。方法:将120只SD大鼠随机分为单次给药组和多次给药组,灌胃透骨消痛胶囊后,根据吸光度与波长曲线下面积(吸波面积)和总固体整体成分的总浓度成正比的特点,采用吸波面积法测定该胶囊中整体药物成分的含量。血药浓度数据用DAS 2.0药动学软件处理,按房室模型拟合并求算单次给药组的药动学参数和多次给药组的稳态血药浓度。结果:透骨消痛胶囊单次给药后,药峰浓度(Cmax)(10.200±0.586)mg·L-1,达峰时间(tmax)(0.515±0.054)h,消除半衰期(t1/2)(1.318±0.049)h,药时曲线下面积(AUC0-24 h)(13.054±0.422)mg·h·L-1;多次给药6 d后血药浓度达稳态,稳态血药浓度(Cav),波动度(DF),稳态药-时曲线下面积(AUCss)分别为(4.073±0.282)mg·L-1,1.166±0.175,(48.878±1.931)mg·h·L-1。结论:透骨消痛胶囊多次给药后整体药物成分的血药浓度变化处于较好的稳态过程,与单次给药的体内行为较一致,说明该制剂临床剂量的确定较为合理。

Comparison of Pharmacokinetic Behavior by Single and Multiple Oral Administration of Tougu Xiaotong Capsules in Rats

Objective: To develop the study on pharmacokinetics of Tougu Xiaotong capsules after single and multiple oral administration in rats,to discuss relevance between plasma concentration and pharmacokinetic parameters in different ways of administration,which provides basis for the clinical rational use of traditional Chinese medicine compound. Method: SD rats were randomly divided into 2 groups,including single and multiple administration group,respectively.After intragastrical administration of Tougu Xiaotong capsules,according to the area under absorbance-wavelength curve (AUAWC) being proportional to the total concentration of total solid overall composition,AUAWC was used to measure overall composition content of the capsules.The blood drug concentration data were processed in DAS 2.0 pharmacokinetic software;after single and multiple oral administration,pharmacokinetic parameter and the steady-state plasma concentration were calculated by compartment model. Result: After single oral administration,C_max was (10.200±0.586) mg·L^-1,t_max was (0.515±0.054) h,t_1/2 was (1.318±0.049) h and AUC_{0-24 h} was (13.054±0.422) mg·h·L^-1,respectively.Steady-state plasma concentration was achieved after 6 d in the multiple oral administration group,C_av was (4.073±0.282) mg·L^-1,DF was 1.166±0.175 and AUC_ss was (48.878±1.931) mg·h·L^-1,respectively. Conclusion: Change of plasma concentration after multiple oral administration of Tougu Xiaotong capsules is in a good steady-state process,it is consistent with in vivo behaviour of the single oral administration group,which shows rationality in the clinical dosage of Tougu Xiaotong capsules.