Plasma isosorbide dinitrate concentrations in human subjects after administration of standard and sustained-release formulations.
After sublingual administration of 5 mg of isosorbide dinitrate, mean plasma concentrations (+/-SD) peaked (8.9+/-3.1 ng/ml) at 15 min after dosing and declined with a half-life of 30 min. After oral administration of 5 mg, mean concentrations peaked (3.1+/-0.7 ng/ml) at 30 min and declined with a half-life of 40 min. After oral administration of 20 mg in a sustained-release tablet, mean concentrations initially peaked (1.4+/-1.2 ng/ml) at 40 min, declining to 0.9+/-0.5 ng/ml after 8 hr. Mean concentrations were maintained above half the mean peak level during 10 hr. Because of probable rapid first-pass metabolism, the bioavailability of isosorbide dinitrate after administration of the oral dose of the standard tablet was 58% of that from the sublingual dose, and the bioavailability from the sustained-release tablet was 47% of that from the sublingual dose of the standard tablet. The time course of mean plasma concentration data could be described by a one-compartment model; but a more complex model, taking the pass effect into account, probably is needed for a better description of the pharmacokinetics of isosorbide dinitrate.
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D003692:Delayed-Action Preparations; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000097:blood*; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D009060:Mouth Floor; D013607:Tablets; D013997:Time Factors
D003692:Delayed-Action Preparations; D013607:Tablets; D007548:Isosorbide Dinitrate