Plasma isosorbide dinitrate concentrations and effect after chewable and high-dose, sustained-release formulations.
Isosorbide dinitrate (ISDN) was given to eight healthy volunteers either as 5 mg chewable ISDN hourly or as 40-mg, slow-release formulation every 8 h. Plasma concentration of ISDN and its two metabolites were measured during one dosing interval at steady state. Mean steady-state plasma concentration (Cpss) during the interval was taken as a measure for bioavailability. Cpss after bucal absorption was similar to that after the sustained-release preparation. Relative bioavailability of the latter reached 111%. The effect of ISDN was measured by digital plethysmography (DPG) during the first dosing interval and after 10 and 48 h, when a steady state had been reached with each formulation. DPG changes were of similar magnitude during the first 10 h, but showed a 30% decrease after 48 h. This tolerance is probably due to physiologic counterregulation. Changes in DPG reflect effects of ISDN which can be used during short-term application of the drug to assess systemic bioavailability. Development of tolerance, however, precludes the use of DPG to assess bioavailability in long-lasting steady-state experiments.
D000328:Adult; D002214:Capsules; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010991:Plethysmography
D002214:Capsules; D003692:Delayed-Action Preparations; D007548:Isosorbide Dinitrate