单硝酸异山梨酯片剂在健康人体的生物等效性

Study on Bioequivalence of the Two Kinds of Isosorbide Mononotrate Tablets in Healthy Volunteers

目的研究单硝酸异山梨酯片的人体和对生物利用皮和生物等效性。方法健康志愿者18名，随机双交叉单剂量口服单硝酸异山梨酯片和参比制剂，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（HPLC）法测定血浆中单硝酸异山梨酯的浓度。用DAS药代动力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（10-24），AUC（0-∞。）和Cmax经方差分析和双单侧t检验，Tmax进行秩和检验。结果单剂量口服单硝酸异山梨酯片和参比制剂后，血浆单硝酸异山梨酯的Cmax分别为（424．28＋43．09）μg·L^-1和（442．48±57．78）μg·L^-1；Tmax分别为（1．11±0．2）h和（1．136±0．24）h；AUC（o-24）分别为（2855．09±276．2）μg·h·L^-1和（3028．28±296．0）μg·h·L^-1；AUC（0-inf）分别为（3046．40±314．61）μg·L^-1和（3312．46±382．60）μg·h·L^-1。AUC（0—24）、AUC（0-∞）、Cmax的90％可信区间分别为90．3％～98．5％、87．2％～97．1％和92．6％～99．9％。结论试验与参比制剂的人体相对生物利用度为（94．79±10．14）％，2制剂具有生物学等效性。

Objective To study the relative bioavailability and bicequivalence of isosorbide mononotrate tablets in healthy volunteers. Methods A single oral dose （40mg of respective test and reference） was given to 18 healthy volunteer in a randomiaed crossover study with an interval of one week. Blood samplings were eouducted consequently within 24 hours; the concentrations of isosorbide monouotrate in plasma were determined by high-performance liquid ehromatoaphy （HPLC）. The relative bioavailability was calcolated and bicequivalence was evaluated by DAS program. Analysis of variance and two one sides t test were used to test AUC（0-24）, AUC（0-∞）,and Cmax. rank test was used to test Tmax. Results After a single oral dose of test and reference preparations, Cmax of isosorbide monouotrate in plasnra was424.28＋43.09μg·L^-1 and 442.48±57.78μg·L^-1, respectively; Tmax was 1.11±0.21h and 1.136±0.24h respectively; AUC （0 - 24） was 2855.09±276.2μg·h·L^-1 and 3028.28±296.0μg·h·L^-1; respeetively; AUC （0- inf） was 3046.40±314.61μg·L^-1 and 3312.46±382.60μg·h·L^-1 respectively. The 90% confidence interval of AUC（0-24）, AUC（0--∞） and Cmax was 90.3% - 98.5%, 87.2%- 97.1% and 92.6% - 99.9% respectively. Condusions The relative bioavailability of test and reference preparations was （94.79 - 10.14）%, the two preparations are bioequivalent.