Use of isosorbide dinitrate saliva concentrations for biopharmaceutical investigations

The concentration of isosorbide dinitrate in paired samples of plasma and mixed saliva was monitored for up to 24 hr after oral administration of 60 mg of sustained-release isosorbide dinitrate to eight healthy volunteers. Measured isosorbide dinitrate plasma concentrations were mainly in the range of 0.1-10 ng/ml. Isosorbide dinitrate was excreted into saliva resulting in a mean (+/- SD) saliva-plasma concentration ratio of 0.68 +/- 0.37. A significant correlation between concentrations of isosorbide dinitrate in saliva and plasma was found (p less than 0.01). The sustained-release properties of the administered formulation were confirmed from the concentrations of isosorbide dinitrate found in both saliva and plasma. Saliva-plasma ratios were independent of the absolute concentrations of isosorbide dinitrate but showed a slight tendency to decrease with time. The principal factor relating saliva and plasma isosorbide dinitrate concentrations appeared to be the degree of plasma protein binding of the drug.