Rietbrock N, Knoll J, Merz P G, Menke G
Dtsch Med Wochenschr. 1985 Nov 22;110(47):1821-5. doi: 10.1055/s-2008-1069095.
The relative bioavailability of isosorbide dinitrate (ISDN) and its mononitrate metabolites (IS-2-MN, IS-5-MN) was determined under repetitive dose conditions in 8 healthy volunteers using a randomised, crossover design. Reference drugs were non-sustained release ISDN (Isoket 20) and IS-5-MN (Ismo 20). The relative bioavailability of ISDN after Iso Mack Retard was 69%, for two development products 78% and 79%, and 87% for Isoket Retard. The bioavailability of IS-2-MN and IS-5-MN in sustained release preparations was 6-16% and 1-17% lower, respectively. Whereas the sum total for the area under the concentration-time curve (ISDN and metabolites) for Iso Mack Retard 20 mg was also significantly lower, there was no significant difference in this parameter between Isoket retard 20 and Isoket 20. Taking IS-5-MN non-retard as reference, the bioavailability of IS-5-MN and total nitrate in all ISDN preparations examined was significantly lower.
在8名健康志愿者中采用随机交叉设计，在重复给药条件下测定了硝酸异山梨酯（ISDN）及其单硝酸代谢产物（IS - 2 - MN、IS - 5 - MN）的相对生物利用度。参比药物为非缓释ISDN（异舒吉20）和IS - 5 - MN（依姆多20）。异乐定缓释片（Iso Mack Retard）后ISDN的相对生物利用度为69%，两种研发产品为78%和79%，异舒吉缓释片（Isoket Retard）为87%。缓释制剂中IS - 2 - MN和IS - 5 - MN的生物利用度分别低6 - 16%和1 - 17%。虽然异乐定缓释片20 mg的浓度 - 时间曲线下面积总和（ISDN和代谢产物）也显著较低，但异舒吉缓释片20与异舒吉20在此参数上无显著差异。以非缓释的IS - 5 - MN为参比，所有受试ISDN制剂中IS - 5 - MN和总硝酸盐的生物利用度均显著较低。
