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目的研究他克莫司片在beagle犬体内的药动学和生物等效性。方法采用随机自身交叉对照实验,将6例beagle犬按照先参比制剂后受试制剂、先受试制剂后参比制剂2种给药序列进行随机分配,每组3例,每个周期单次口服3 mg参比制剂或受试制剂,用LC-MS/MS测定样品浓度,再采用Win Nonlin 6.3版软件计算药动学参数,比较受试制剂和参比制剂的生物等效性。结果受试制剂和参比制剂他克莫司药动学参数Tmax分别为(1.08±0.41)h和(0.83±0.13)h,Cmax分别为(11.63±1.35)ng·mL~(-1)和(14.83±4.70)ng·mL~(-1),AUC0-48分别为(62.93±32.06)h·ng·mL~(-1)和(62.89±28.14)h·ng·mL~(-1),半衰期t1/2分别为(10.90±4.26)h和(10.99±3.12)h。Beagle犬口服受试制剂后Tmax,t1/2在受试制剂和参比制剂间无明显差异;峰浓度Cmax约为参比制剂给药后的85.34%,90%置信区间为87.21%~102.16%;相对生物利用度(AUClast,受试/AUClast,参比)为99.42%,90%置信区间为85.53%~115.56%,表明受试制剂和参比制剂较接近。结论他克莫司缓释胶囊受试制剂和参比制剂具有生物等效性。
Objective To study the pharmacokinetics and bioequivalence of tacrolimus in beagle dogs. Methods Six randomized crossover experiments were conducted in six beagle dogs randomly assigned to two groups according to the first reference preparation and the second reference preparation. Each group consisted of three cases with single cycle Oral administration of 3 mg of reference formulation or test preparation, LC-MS / MS determination of the concentration of the sample, and then using Win Nonlin 6.3 software to calculate the pharmacokinetic parameters of the tested formulations and reference bioequivalence. Results The pharmacokinetic parameters of tacrolimus in test and reference preparations were (1.08 ± 0.41) h and (0.83 ± 0.13) h, respectively, with Cmax of (11.63 ± 1.35) ng · mL -1 and (14.83 ± 4.70) ng · mL -1, (62.93 ± 32.06) h · ng · mL -1 and (62.89 ± 28.14) h · ng · mL -1 for AUC0-48, , The half-life t1 / 2 were (10.90 ± 4.26) h and (10.99 ± 3.12) h, respectively. After oral administration of Beagle dogs, Tmax and t1 / 2 showed no significant difference between the tested and reference preparations; the peak concentration Cmax was about 85.34% and the 90% confidence interval was 87.21% -102.16% after the reference formulation was administered. ; Relative bioavailability (AUClast, test / AUClast, reference) was 99.42%, 90% confidence interval was 85.53% ~ 115.56%, indicating that the test preparation and the reference preparation are closer. Conclusion Tacrolimus sustained-release capsules are bioequivalent to the test and reference preparations.