[Comparative pharmacokinetics and bioavailability of isosorbide dinitrate and its metabolites isosorbide 5- and...

The present comparative pharmacokinetic study performed to establish the relative bioavailability for an isosorbide dinitrate (ISDN) retard preparation (Sorbidilat-retard) included 6 healthy, male and female volunteers. In a randomised cross-over scheme the volunteers received a capsule Sorbidilat retard forte and a tablet of a standard preparation which contained as well 40 mg isosorbide dinitrate as retard formulation. Blood samples were taken over a period of 24 h and isosorbide dinitrate, 5-isosorbide mononitrate and 2-isosorbide mononitrate measured in the serum by means of gas chromatography with electron-capture detection. The resorption rate for all three substances revealed only minor differences between Sorbidilat and the standard preparation. However, the slightly retarded absorption for the compound from Sorbidilat with a longer period of invasion led to a higher maximal concentration and to higher serum levels of ISDN and the mononitrates over the whole period of observation. The relative bioavailability for all three substances ISDN, 5-isosorbide mononitrate and 2-isosorbide mononitrate, was estimated from the areas under the plasma concentration-time curves and was 2 to 2.5 fold higher for the Sorbidilat preparation than for the standard preparation.