Bioavailability of isosorbide dinitrate and its two mononitrate metabolites from sustained-release formulations.

Plasma concentrations and bioavailability of isosorbide dinitrate (ISDN) and its active metabolites isosorbide 2-mononitrate (2-ISMN) and isosorbide 5-mononitrate (5-ISMN) from two sustained-release formulations and one standard-release formulation of isosorbide dinitrate were compared. Means of peak drug concentrations of ISDN, 2-ISMN, and 5-ISMN after administration of the 20-mg sustained-release formulation were 5.5, 24.4, and 129.1 ng/ml, respectively, at 3.1, 4.2, and 4.5 h; after the 40-mg sustained-release formulation, they were 10.9, 44.0, and 214.5 ng/ml, respectively, at 4.2, 6.3, and 6.7 h; and after the 20-mg standard formulation, they were 19.1, 34.7, and 159.2 ng/ml, respectively, at 0.5, 1.0, and 1.5 h. As might be expected, peak concentrations and their times of occurrence were statistically significantly different when results from the sustained-release formulation were compared to those from the standard formulation. Plasma drug concentrations were detectable for longer after administration of the sustained-release formulations. The extent of bioavailability of ISDN, 2-ISMN, and 5-ISMN from the three formulations as estimated from the areas under the plasma drug concentration - time curves were not statistically significantly different (p greater than 0.05). The ratios for relative drug bioavailability from the respective formulations were similar whether ISDN, 2-ISMN, or 5-ISMN data were used for calculation. Reasons are discussed for the biphasic decline of plasma ISDN concentrations (half-lives 26 min and 5.1 h) obtained after administration of the standard-release formulation.