Isosorbide 5-mononitrate kinetics

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Abstract
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, t½ 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 t½ was 19 ± 12 min. Unlike other vasodilator organic nitrates in clinical use, 5‐ISMN is notable for its relatively long t½, essentially complete oral absorption, lack of active metabolites, and low intersubject variability in kinetics. Clinical Pharmacology and Therapeutics (1984) 35, 653–659; doi:10.1038/clpt.1984.90