盐酸曲美他嗪片的人体生物等效性研究

 目的研究盐酸曲美他嗪片的人体相对生物利用度和生物等效性。方法健康志愿者20名,随机双交叉单剂量国产盐酸曲美他嗪片(受试制剂)和进口盐酸曲美他嗪片(参比制剂),剂量分别为40mg,剂间间隔为1周。分别于服药后24h内多点抽取静脉血;用高效液相色谱法测定血浆中曲美他嗪的浓度。用DAS药动学程序计算相对生物利用度并评价两种制剂生物等效性。AUC_0-24,AUC_0-inf和ρ_max经方差分析和双单侧t检验,t_max进行秩和检验。结果单剂量口服盐酸曲美他嗪片受试和参比制剂后,血浆的曲美他嗪的ρ_max分别为(122.78±11.60)和(115.12±10.98)μg·L^-1;t_max分别为(2.08±0.34)和(2.13±0.39)h;AUC_0-24分别为(962.56±122.03)和(914.53±86.16)μg·h·L^-1;AUC_0-inf分别为(1004.71±125.94)和(966.40±99.53)μg·h·L^-1。AUC_0-24的90%可信区间为100.4%～109.5%,AUC_0-inf的90%可信区间为99.1%～108.4%,ρ_max的90%可信区间为102.6%～110.8%。结论两制剂的人体相对生物利用度为(105.41±11.22)%,两者具有生物等效性。

Study of the Bioequivalence of Trimetazidine Hydrochloride Tablets in Chinese Healthy Volunteers

OBJECTIVE To study the relative bioavailability and bioequivalence of Trimetazidine Hydrochloride Tablets in healthy volunteers.METHODS A single oral dose(40 mg of tested and reference formulation)was given to 20 healthy volunteers in a randomised crossover study.The concentrations of Trimetazidine in plasma were determined by HPLC.The pharmacokinetic parameters were calculated and the bioavailability and bioequivalence of two formulations were evaluated by DAS program.RESULTS After a single dose,the pharmacokinetic parameters for Trimetazidine were as follows:ρ_max were(122.78±11.60)and(115.12±10.98)μg·L^-1;t_max were(2.08±0.34)and(2.13±0.39)h;AUC_0-24 were(962.56±122.03)and(914.53±86.16)μg·h·L^-1;AUC_0-inf were(1 004.71±125.94)and(966.40±99.53)μg·h·L^-1 for tested and reference formulation,respectively.The 90% confidential interval of AUC_0-24,AUC_0-inf and ρ_max of tested formulation were 100.4%～109.5%,99.1%～108.4% and 102.6%～110.8%,respectively.CONCLUSION The relative bioavailability is(105.41±11.22)%.The results of the statistic analysis show that the two formulations are bioequivalent.