SINGLE AND MULTIPLE-DOSE PHARMACOKINETIC STUDIES OF ORAL SUSTAINED-RELEASE AND NONSUSTAINED RELEASE FORMULATIONS OF ISOSORBIDE-5-MONONITRATE IN HEALTHY-VOLUNTEERS

The pharmacokinetics of a new sustained release tablet (40 mg, ''test' ') of isosorbide-5-moninitrate (CAS 16051-77-7, IS-5-MN) was investiga ted together with a reference preparation (20 mg, ''reference'') after single and multiple oral administration in ten healthy human subjects using an open, randomised two-way crossover experimental design. Base d on the statistical evaluation of the area under the plasma concentra tion-time curve (AUC), the two tablet formulations are judged to be th e same with regard to the amount absorbed. Pharmacokinetic data showed that with the test tablet significantly lower and delayed mean peak p lasma levels (C-max) were reached compared with the reference preparat ion in both single and multiple dose studies. The test formulation als o produced lower minimum plasma concentration (C-min). However, there was no statistically significant difference for other pharmacokinetic parameters, including the elimination rate constant (K-el), the elimin ation half-life (t(1/2)) and the peak-trough fluctuation constant (PTF ) between the two treatments. It was demonstrated that the new sustain ed release formulation of isosorbide-5-mononitrate could be useful in clinical practice for the treatment of angina pectoris and congestive heart failure.