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目的:研究单硝酸异山梨酯滴丸的人体相对生物利用度和生物等效性。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滴丸(试验制剂)和胶囊(参比制剂),剂量分别为40mg,剂间间隔为1周。分别于服药后36h内多点抽取静脉血;用高效液相色谱法测定血浆中单硝酸异山梨酯的浓度。用DAS药动学程序计算相对生物利用度并评价2种制剂生物等效性。AUC(0-36),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试验和参比制剂后,血浆单硝酸异山梨酯的Cmax分别为(453.2±67.4)μg.L-1和(434.3±63.2)μg.L-1;tmax分别为(0.60±0.13)h和(0.69±0.14)h;AUC(0-36)分别为(3013.7±576.3)μg.h.L-1和(2974.2±754.4)μg.h.L-1;AUC(0-∞)分别为(3156.0±582.8)μg.h.L-1和(3161.1±766.5)μg.h.L-1。AUC(0-36)、AUC(0-∞)、Cmax的90%可信区间分别为95.8%～108.9%,94.8%～106.6%和100.5%～108.2%。试验与参比制剂的人体相对生物利用度为(103.4±16.9)%。结论:两制剂具有生物学等效性。
Objective: To study the relative bioavailability and bioequivalence of isosorbide mononitrate dripping pills. Methods: Eighteen healthy volunteers were randomized double crossover single dose oral administration of isosorbide mononitrate dripping pills (test preparation) and capsules (reference preparation) at dosages of 40 mg and dosing interval of 1 week. Venous blood samples were drawn for more than 36 hours after taking the drug. The concentration of isosorbide mononitrate in plasma was determined by high performance liquid chromatography. Relative bioavailability was calculated using the DAS pharmacokinetic program and the bioequivalence of the two formulations was evaluated. AUC (0-36), AUC (0-∞) and Cmax were analyzed by ANOVA and double unilateral t-test, tmax for rank sum test. Results: The single-dose oral administration of isosorbide mononitrate test and reference preparation, the plasma Cmax of isosorbide mononitrate were (453.2 ± 67.4) μg.L-1 and (434.3 ± 63.2) μg.L-1, respectively; tmax (0.60 ± 0.13) h and (0.69 ± 0.14) h respectively; AUC (0-36) were (3013.7 ± 576.3) μg.hL-1 and (2974.2 ± 754.4) μg.hL- ∞) were (3156.0 ± 582.8) μg.hL-1 and (3161.1 ± 766.5) μg.hL-1, respectively. The 90% confidence intervals of AUC (0-36), AUC (0-∞) and Cmax were 95.8% -108.9%, 94.8% -106.6% and 100.5% -108.2%, respectively. The relative bioavailability of test and reference preparations was (103.4 ± 16.9)%. Conclusion: The two preparations have biological equivalence.