Plasma concentrations of isosorbide dinitrate and mononitrates after acute and chronic oral administration of isosorbide dinitrate in man.

Isosorbide dinitrate (Cedocard) was given orally to patients in doses of either 5, 20 or 40 mg t.i.d. for 19 days, and the plasma concentrations of unchanged product and of its mononitrates were measured. While the concentration of isosorbide 2-mononitrate remained stable, the concentration of isosorbide dinitrate and of isosorbide 5-mononitrate in plasma increased gradually during the first days of administration. Decrease in presystemic or systemic clearance is probably responsible for this phenomenon.