[Pharmacodynamic effects of the sustained-release tablet of isosorbide dinitrate and its bioavailability in conscious dogs (author's transl)].

Oral administration of isosorbide dinitrate (ISDN), 1 approximately 2 mg/kg, resulted in a dose-dependent decrease in the pulse pressure by reducing the systolic pressure and slightly elevating the diastolic pressure in conscious dogs. Therefore, this system was employed to evaluate the effectiveness of the sustained-release ISDN tablet as compared with that of the standard tablet. Four standard tablets (20 mg of ISDN) given in a single dose significantly decreased the pulse pressure, which became lowest at 2 hr after administration and returned to the near original level at 6 hr. On the other hand, with four sustained-release tablets (80 mg of ISDN) 4 hr was required to produce a maximum decrease, and at 10 hr, the pulse pressure was still much lower than the original level. The plasma concentration of ISDN was measured by a gas chromatographic method. The time course of the plasma concentration of ISDN after administration of each preparation was correlated with that of the decrease in the pulse pressure. This suggests that the system employed is useful in evaluating the bioavailability of various preparations of organic nitrates (ISDN). In addition, these data demonstrate that the sustained-release formulation of ISDN possesses a prolonged pharmacological effect.