[Dose-dependent Serum Concentration of ISDN and Its Metabolites Following Administration of ISDN-retard. Studies Under Steady-state Conditions]

In a randomized cross-over trial of four groups of patients (total 49 patients) the serum concentrations of isosorbide dinitrate (ISDN), isosorbide-2-mononitrate (IS-2-MN) and isosorbide-5-mononitrate (IS-5-MN) were measured under steady-state conditions after administration of 20, 40, 60 and 80 mg, respectively, of two ISDN preparations, the two being bioequivalent. At the studied dosage there was a linear relationship between dose and serum concentration of ISDN and its two metabolites in the proportion of 1:6:70. Because the serum concentration of IS-5-MN is so high under steady-state conditions, there is the potential problem of tolerance developing. The drug should therefore be administered at a lower dose twice daily.