MULTIPLE DOSE PHARMACOKINETIC AND BIOAVAILABILITY STUDIES OF ORAL SUSTAINED RELEASE AND CONVENTION

The pharmacokinetics of a new sustained release tablets (40 mg, qd) of isosorbide5mononitrate (IS5MN) was investigated together with a conventional preparation (20 mg, bid) after multiple oral administration in ten healthy human subjects using an open, randomized twoway crossover experimental design. Based on three statistical analyses of the area under the plasma concentrationtime curve (AUC), the two tablet formulations are judged to be bioequivalent (P>01), with a relative bioavailability of 10895% for the IS5MN sustained release formulation. Pharmacokinetic data showed that the sustained release formulation reached mean peak plasma levels significantly later and lower minimum plasma concentration (Cmin), compared with the conventional preparation. But no statistically significant difference was found for other pharmacokinetic parameters including peak plasma levels (Cmax), AUC, elimination constant (Ke), elimination halflife (T1/2) and fluctuation index (FI) between the two preparations (P>005).