5-单硝酸异山梨酯缓释胶囊的人体相对生物利用度、释放度及药代动力学

Dissolution,Pharmacokinetics and Relative Bioavailability on Sustained-Release Capsule of Isosorbide-5-Mononitrate

目的 研究我国珠海和德国两家药厂研制的两种长效异乐定 5 0胶囊的人体相对生物利用度、释放度及药代动力学。方法 采用气相色谱法测定 2 1名健康志愿者血浆中 5 单硝酸异山梨酯 (5 ISMN)的浓度 ,采用液相色谱法测定释放度 ,计算两者的药代动力学参数、相对生物利用度。结果 口服 5 ISMN缓释试验胶囊后的药动学参数分别为 :tmax为 (5 .6 2± 0 .5 0 )h ,ρmax为 (4 5 0 .0 4± 95 .0 2 )ng/mL ,MRT为 (10 .85± 0 .79)h ,T1/ 2 为(6 .48± 0 .89)h ,AUC0～ 3 6h为 (6 90 5 .6 8± 130 0 .0 0 )ng/(mL·h) ,AUC0～∞ 为 (712 1.2 8± 135 4.78)ng/(mL·h) ;口服 5 ISMN缓释参比胶囊后的药动学参数分别为 :tmax为 (5 .5 7± 0 .75 )h ,ρmax为 (4 5 7.13± 98.0 0 )ng/mL ,MRT为 (10 .95± 0 .79)h ,T1/ 2 为 (6 .5 7± 0 .96 )h ,AUC0～ 3 6h为 (712 2 .0 2± 1439.90 )ng/(mL·h) ,AUC0～∞ 为(736 6 .6 8± 15 2 3.30 )ng/(mL·h)。结论 试验胶囊的AUC与参比胶囊相比 ,无显著性差异 ,试验胶囊与参比胶囊生物等效。试验胶囊平均相对生物利用度为 (98± 11) % (n =2 1,以AUC0～T计算 )。将试验胶囊和参比胶囊的药动学参数进行方差分析 。

Purpose: To study the dissolution, pharmacokinetics, relative bioavailability of the sustained-release capsule in vitro and vivo. Methods: The concentration of isosorbide-5-mononitrate (5-ISMN) in vitro was determined by HPLC and the concentration in serum of 21 volunteers was determined by GC. Results: tmas of experiment capsule and the contrast one was (5.62 ± 0.50) h and (5.57 ± 0.75) h, ρmax was (450.04 ± 95.02) ng/mL and (457.13 ± 98.00) ng/mL,MRT was (10.85 ± 0.79) h and (10.95 ± 0.79) h, T1/2 was (6.48 ± 0.89) h and (6.57 ± 0.96) h,AUC0-36 h was (6 905.68 ± 1 300.00) ng/ (mL&middoth) and (7 122.02 ± 1439.90) ng/(mL&middoth),AUC 0-∞ was (7 121.28 ± 1354.78) ng/(mL&middoth) and (7 366.68 &middot 1 523.30) ng/(mL&middoth). Conclusions: The results of statistical analysis showed that the two formulations were bioequivalent. The relative bioavailability was (98 ± 11) %.