盐酸曲美他嗪片的人体生物等效性研究

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

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。AUC0-24,AUC0-inf和ρmax经方差分析和双单侧t检验,tmax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ρmax分别为(122.78±11.60)和(115.12±10.98)μg.L-1;tmax分别为(2.08±0.34)和(2.13±0.39)h;AUC0-24分别为(962.56±122.03)和(914.53±86.16)μg.h.L-1;AUC0-inf分别为(1004.71±125.94)和(966.40±99.53)μg.h.L-1。AUC0-24的90%可信区间为100.4%～109.5%,AUC0-inf的90%可信区间为99.1%～108.4%,ρmax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。

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： ρmax were （ 122.78±11.60） and （ 115.12±10.98） μg·L^1-; ρmax were （2.08±0.34） and （2.13±0.39）h; AUC0-24 were （962.56 ±122.03） and （914.53±86.16）μg·h ·L^-1; AUC0-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 AUC0-24, AUC0-inf and ρmax of tested formulation were 100.4% - 109.5% ,99.1% ～ 108.4% and 102.6% ～ ll0.8% ,respectively. CONCLUSION The relative bioavailability is （105.41 ± ll.22）%. The results of the statistic analysis show that the two formulations are bioequivalent.