维A 酸软胶囊在中国健康受试者体内的药动学研究

目的采用单剂量交叉实验设计，考察30名健康受试者口服维A酸软胶囊受试制剂及其参比制剂20mg后的生物等效性研究。方法建立LC—MS／MS法测定血浆中维A酸的浓度。采用C18柱，阿维A酸为内标，以多反应监测（MRM）模式监测。结果两种制剂的Cmax、Tmax、AUC0→10和AUC0→∞（均数±标准差）分别为：（142．52±34．09）和（141．75±31．64）ng．mL^-1；（2．1±0．3）和（2．05±0．36）h；（352.67±121.78）和（343．95±100．70）ng·h·mL^-1；（353．91±120．71）和（345．67±98．96）ng·h·mL^-1试验制剂对参比药物的相对生物利用度F为（101．6％±18.5％）；校正后维A酸的主要药代动力学参数Cmax、Tmax、AUC0→10和AUC0→∞（均数±标准差）分别为：（141．59±34．09）和（140．79±31．64）ng．mL^-1；（2．07±0．29）和（2．05±0．36）h；（343．19±121．56）和（334．11±100．32）ng．h．mL^-1；（344．11±121．58）和（335．09±100．26）ng．h．mL^-1。结论试验药物对参比药物的相对生物利用度F为（101．7％±19．1％）（以AUC0→10作为评价依据），两者具有生物等效性。

Pharmacokinetics of Tretinoin Soft Capsules in Chinese Healthy Volunteers

Objective The pharmacokinetics of tretinoin test and reference soft capsules which were orally administrated by 30 healthy volunteers was investigated. Methods A LC-MS/MS method was established for the determination of tretinoin in plasma. A C18 column was used with acitretin as the internal standard. The analytes were detected in the positive ion mode and multiple reactions monitoring （MRM）. Results The Cmax, Tmax AUC0 →10 and AUC0→∞ （average ± SD） of test capsules and reference capsules were 142.52 ± 34.09 ng.mL-1 and 141.75 ± 31.64 ng.mL^-1, 2.1 ± 0.3 h and 2.05±0.36 h, 352.67± 121,78 ng.h.mL^-1 and 343.95 ± 100.70 ng.h.mL 1 353.91 ± 120.71 ng.h.mL ^-1 and 345.67±98.96 ng.h.mL 1, respectively. The relative bioavailability of tretinoin soft capsules was 101.6 % ± 18.5 %. The C T AUC0→10 and AUC0→∞ （average ± SD） of test capsules and reference capsules after baseline being corrected were 141.59 ± 34.09 ng.n^-1 1 and 140.79 ± 31.64 ng.mL^-1, 2.07 ± 0.29 h and 2.05 ± 0.36 h, 343.19 ± 121.56 ng-h.mL^-1 and 334.11±100.32 ng.h.mL^-1 344.11 ± 121.58 ng.h.mL^-1 and 335.09 ±100.26 ng.h-mL^-1, respectively. Conclusion The relative bioavailabiliW of tretinoin soft capsules was 101.7% ± 19.1%. No significant difference was observed in the rate and degree of absorption, which indicated that the two preparations were bioequivalent.