Bennett B M, Twiddy D A, Moffat J A, Armstrong P W, Marks G S
Biochem Pharmacol. 1983 Dec 15;32(24):3729-34. doi: 10.1016/0006-2952(83)90142-9.
Isosorbide dinitrate (ISDN) (at a concentration of 100 ng/ml) was incubated aerobically at 37 degrees in whole blood from five male and five female normal volunteers. Following incubation of the blood samples for 0, 30, 60, 120, 240 and 360 min, the samples were centrifuged and the plasma was assayed for ISDN. A linear relationship was observed between the logarithm of the concentration of ISDN remaining and incubation time, and there was a significant difference between the T1/2 of ISDN in blood from males (90.6 min) and females (161.4 min). Very little ISDN metabolism was observed when ISDN was incubated with plasma rather than whole blood. When erythrocytes, resuspended in saline, were incubated with ISDN, there was a time-dependent loss of ISDN from the saline incubation medium. Investigation of the soluble fraction obtained after hemolysis of these erythrocytes also showed a time-dependent loss of ISDN. The saline incubation medium contained sufficient concentrations of the two major ISDN metabolites (isosorbide 2- and 5-mononitrate) to account for the observed disappearance of ISDN. The results indicate that ISDN is metabolized in the cellular compartment of blood and that the metabolic rate in males is greater than that in females.
将硝酸异山梨酯（ISDN）（浓度为100 ng/ml）与来自五名男性和五名女性正常志愿者的全血在37℃有氧条件下孵育。血液样本孵育0、30、60、120、240和360分钟后，离心样本并测定血浆中的ISDN。观察到剩余ISDN浓度的对数与孵育时间之间呈线性关系，并且男性血液中ISDN的半衰期（90.6分钟）与女性血液中ISDN的半衰期（161.4分钟）之间存在显著差异。当ISDN与血浆而非全血孵育时，观察到的ISDN代谢极少。当用盐水重悬的红细胞与ISDN孵育时，盐水孵育介质中ISDN随时间减少。对这些红细胞溶血后获得的可溶部分的研究也显示ISDN随时间减少。盐水孵育介质中含有足够浓度的两种主要ISDN代谢物（异山梨醇2-单硝酸盐和5-单硝酸盐），可以解释观察到的ISDN消失情况。结果表明，ISDN在血液的细胞部分被代谢，并且男性的代谢率高于女性。
