A COMBINED SINGLE AND MULTIPLE DOSE PHARMACOKINETIC STUDY OF ORAL ISOSORBIDE-5-MONONITRATE IN HEALTHY-VOLUNTEERS

Pharmacokinetics of 20 mg isosorbide-5-mononitrate (IS-5-MN) after single and multiple administration of two different tablet formulations were investigated in twelve healthy human subjects using an open, randomized, two-way crossover experimental design. Pentacard(R) 20 mg tablets were compared with Ismo(R) 20 mg tablets. After single-dose administration, both preparations caused a rapid increase in IS-5-MN plasma levels with the peak plasma concentration occurring between 0.5 and 1.5 h. For both formulations, the mean plasma half-life was found to be approximately 5 h after a single dose. In steady state during multiple dosing (t.i.d. at 8 h dosing intervals), a reduced elimination rate was observed. In line with this observation, the area under the plasma concentration-time curve (AUC) for one 8 h dosing interval during multiple dosing was higher than the extrapolated AUC after a single dose. Based on statistical evaluation of the various relevant pharmacokinetic parameters calculated from the plasma concentrations occurring after single and multiple dosing, the tablet formulations are judged to be bioequivalent.