Relationship between the pharmacodynamics and pharmacokinetics of two oral sustained-release formulations of isosorbide dinitrate in normal man

The relationship between the pharmacodynamics and pharmacokinetics of isosorbide dinitrate (ISDN) following oral administration of 40 mg of two sustained-release formulations was investigated using two different models. A model assuming an additive contribution of all active drug-related substances in plasma to pharmacological effect, i.e., finger pulse plethysmography, resulted in estimates of relative potencies of ISDN:2-MN:5-MN (2-MN:2-isosorbide mononitrate; 5-MN:5-isosorbide mononitrate) as being 1:0.1:0.025. The data analysis using a receptor model (plasma concentration-effect curves) yielded sigmoid curves for 2-MN and 5-MN with similar relative potencies in the range of 20-80% of maximum response providing an upper limit for the pharmacodynamic effect due to ISDN, 2-MN or 5-MN in healthy volunteers.