[Bioavailability of isosorbide dinitrate and isosorbide-5-mononitrate under steady-state conditions]

The relative bioavailability of isosorbide dinitrate (ISDN) and its mononitrate metabolites (IS-2-MN, IS-5-MN) was determined under repetitive dose conditions in 8 healthy volunteers using a randomised, crossover design. Reference drugs were non-sustained release ISDN (Isoket 20) and IS-5-MN (Ismo 20). The relative bioavailability of ISDN after Iso Mack Retard was 69%, for two development products 78% and 79%, and 87% for Isoket Retard. The bioavailability of IS-2-MN and IS-5-MN in sustained release preparations was 6-16% and 1-17% lower, respectively. Whereas the sum total for the area under the concentration-time curve (ISDN and metabolites) for Iso Mack Retard 20 mg was also significantly lower, there was no significant difference in this parameter between Isoket retard 20 and Isoket 20. Taking IS-5-MN non-retard as reference, the bioavailability of IS-5-MN and total nitrate in all ISDN preparations examined was significantly lower.