国产和进口单硝酸异山梨酯缓释胶囊单次和多次给药的人体药动学(英文)

Pharmacokinetics of domestic and imported isosorbide mononitrate sustained-release capsule following a single and multiple dose in healthy volunteers

目的 :比较国产和进口单硝酸异山梨酯缓释胶囊的人体药动学和相对生物利用度。方法 :采用单次和多次给药的 4周期双交叉设计 ,气相色谱 电子捕获检测法 (GC ECD)测定 2 2名健康男性志愿者血浆中单硝酸异山梨酯的浓度。结果 :单次 (2 5mg)口服国产和进口单硝酸异山梨酯缓释胶囊后的药动学参数分别为 :Tmax为 (5 .7±s 0 .5 )h和 (5 .8±1 .0 )h ,Cmax为 (2 3 6± 62 ) μg·L-1和 (2 42± 62 )μg·L-1,T1/ 2 为 (8.3± 1 .6)h和 (8.4± 2 .1 )h ,AUC0 3 6为 (3 .7± 0 .9)mg·h·L-1和 (3 .6±0 .9)mg·h·L-1,AUC0 ∞ 为 (4 .0± 0 .9)mg·h·L-1和 (3 .8± 0 .8)mg·h·L-1,平均滞留时间MRT为 (1 1 .5±0 .8)h和 (1 1 .4± 0 .7)h。多次 (2 5mg,6d)口服国产和进口单硝酸异山梨酯缓释胶囊后的稳态药动学参数分别为 :Tmax 为 (5 .2± 0 .7)h和 (5 .4±0 .9)h,Cmax为(3 1 4± 67) μg·L-1和 (3 1 0± 5 8) μg·L-1,Cmin为(63± 1 4) μg·L-1和 (65± 1 6) μg·L-1,稳态血药浓度均值Cav为 (1 87± 3 8) μg·L-1和 (1 83± 3 8) μg·L-1,AUC0 3 6h为 (5 .0± 1 .0 )mg·h·L-1和 (4 .9± 1 .0 )mg·h·L-1,波动度DF为 (1 3 4± 2 0 )%和 (1 3 4± 1 8) %。

AIM: To compare the pharmacokinetics and relative bioavailability of the domestic and imported sustained release capsules of isosorbide mononitrate (ISMN) in healthy volunteers. METHODS : The study was performed by an open label, single dose and multiple dose, four period crossover design. The plasma drug concentrations of twenty two male healthy volunteers were determined by gas chromatography with electron captured detector method(GC ECD). RESULTS: The pharmacokinetic parameters after a single oral dose of the domestic and imported ISMN capsules were (5.7± s 0.5) h and (5.8±1.0) h for T max , (236±62) μg·L -1 and (242±62) μg·L -1 for C max , (8.3±1.6) h and ( 8.4 ±2.1) h for T 1/2 , (3.7±0.9) mg·h·L -1 and ( 3.6 ±0.9) mg·h·L -1 for AUC 0 36 , (4.0±0.9) mg·h·L -1 and (3.8±0.8) mg·h·L -1 for AUC 0 ∞ , (11.5±0.8) h and (11.4±0.7) h for mean residence time (MRT), respectively. The steady state pharmacokinetic parameters after multiple doses of the domestic and imported ISMN capsules were (5.2±0.7) h and (5.4±0.9) h for T max ,(314±67) μg·L -1 and (310±58) μg·L -1 for C max ,(63±14) μg·L -1 and (65±16) μg·L -1 for C min , (187±38) μg·L -1 and (183±38) μg·L -1 for mean value of steady plasma drug concentration ( C av ),(5.0±1.0) mg·h·L -1 and (4.9±1.0) mg·h·L -1 for AUC 0 36 , (134±20) % and (134±18) % for degree of fluctuation (DF), respectively. The relative bioavailability of the domestic ISMN capsule to the imported ISMN capsule following a single and multiple dose was (103±11) % and (102±9) %, respectively. Main pharmacokinetic parameters between the two formulations in both single and multiple dose studies showed no statistical difference ( P >0.05). CONCLUSION: The result of two one side t test shows that the two formulations are bioequivalent.