5-单硝酸异山梨醇酯缓释胶囊在中国健康男青年的药物动力学(英文)

Pharmacokinetics of sustained-release capsule of 5-isosorbide mononitrate in 20 healthy Chinese young men

目的:比较国产和进口5-单硝酸异山梨醇酯缓释胶囊在健康人体内的药动学。方法:20名志愿者交叉随机分两组,口服50mg,GC-ECD测血药浓度,一室模型拟合或梯形法求药动学参数。结果:多剂量组连续5天服国产或进口胶囊,药动学参数C_(max)分别为(677±103)和(702±76)μg·L^(-1);T_(max)分别为(5.1±2.0)和(5.6±1.3)h;MRT分别为(11.5±0.5)和(11.4±0.7)h;AUC_(0-∞)分别为 (12121±1346)和(12352±988)μg·h·L^(-1),两者差异无显著性(P>0.05)。两种胶囊在服药16h后,血药浓度降至产生耐受性的阈值浓度以下(<300μg·L^(-1))。两种胶囊体内吸收分数和其体外相应时间的溶出率均呈显著正相关(P<0.05),单剂量和多剂量下国产对进口胶囊的相对生物利用度分别为96％±11％和98％±10％。结论:两种胶囊药动学特点相似。

AIM: To compare the pharmacokinetics of domestic and imported sustained-release capsule of 5-isosorbide mononitrate (5-IM). METHODS: A single and 5-d-repeated oral doses of 5-IM 50 mg were performed on 2 groups of 20 Chinese healthy subjects (10 subjects for each group) in a randomized crossover protocol. The 5-IM in plasma were measured by gas chromatography with electron-captured detector method. Data were analyzed automatically by using a CAPP program on a PC computer. RESULTS: Fitting the 5-M concentration-time curves to one-compartment model or following trapezoidal rule, the paramaters such as Tmax, Cmax, Ke, MRT, and AUC were calculated and there were no significant differences between the two kinds of capsule. The major pharmacokinetic parameters of domestic and imported 5-IM sustained-release capsule with a 5-d multiple dose were respectively: Cmax (677 ±103) and (702 ± 76) μg·L-1; Tmax(5.1±2.0) and (5.6±1.3) h; MRT (11.5 ± 0.5) and (11.4±0.7) h; AUC0-∞(12 121 ± 1346) and (12 352 ± 988) μg·h ·L-1. The fraction of drug absorbed in vivo was correlated well with the percentage amount of drug released in vitro at corresponding time ( P < 0.05), and the fluctuation indices on d 5 in multiple dose study were not significantly different between the two formulations (P > 0.05). The relative bioavailability of the domestic capsule for single and multiple dosewere 96 % ± 11 % and 98 % ±10 %, respectively. CONCLUSION: Domestic 5-M sustained-release capsule showed bioequivalence compared with the imported capsule and provided the same nitrate-low interval in the latter part of the 24-h dosing interval.