Isosorbide 5-mononitrate kinetics.

The kinetics of isosorbide 5-mononitrate (5-ISMN) were studied in 12 healthy subjects after intravenous infusion and oral doses of 20 mg. Kinetic parameters calculated by model-independent methods or by assumption of a one-compartment open model were in good agreement. Mean (+/- SD) systemic clearance of 5-ISMN was 127 +/- 21 ml/min, volume of distribution was 48.5 +/- 6.1 l, t 1/2 was 4.4 +/- 0.5 hr, and mean residence time was 6.2 +/- 0.7 hr. At the end of intravenous infusion of 5-ISMN at a rate of 8 mg/hr for 2.5 hr, mean plasma drug concentrations reached 356 +/- 39 ng/ml. Oral doses of 5-ISMN were essentially completely absorbed (93% +/- 13% systemic availability), and mean peak plasma drug concentrations of 388 +/- 70 ng/ml occurred at 0.83 +/- 0.46 hr. Mean absorption t 1/2 was 19 +/- 12 min. Unlike other vasodilator organic nitrates in clinical use, 5-ISMN is notable for its relatively long t 1/2, essentially complete oral absorption, lack of active metabolites, and low intersubject variability in kinetics.