Abstract
Isosorbide dinitrate (ISDN) was introduced into therapy more than 30 years ago as a longer-acting nitrate than nitroglycerin, suitable not only for coping with acute anginal attacks after s.l. administration, but also for prophylactic treatment after oral administration. In order to prolong its antianginal activity further, while at the same time decreasing side effects, several sustained release formulations were developed for oral therapy. In 1972, however, Needleman et al. seriously questioned the oral efficacy of organic nitrates on the basis of experiments in anesthetized rats according to which ISDN and a number of other nitrates used therapeutically should be completely degraded into inactive metabolites during the first pass of the liver. These findings stimulated several groups to reinvestigate the pharmacokinetics and pharmacodynamics of ISDN and its metabolites. In the following our data on pharmacokinetics of ISDN and its main metabolite isosorbide-5-mononitrate (IS-5-MN), which were gathered during the fast 6 years, will be briefly summarized and discussed in the context of the literature concerned.
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