Pharmacokinetics of intravenous and oral isosorbide-5-mononitrate

Abstract

The pharmacokinetics of isosorbide-5-mononitrate (IS-5-MN) has been studied in two groups of healthy volunteers after oral (n=20) and intravenous (n=11) administration of 20 mg, which had previously been proved to be as effective as 20 mg sustained-release isosorbide dinitrate (ISDN). IS-5-MN in serum was measured by gas chromatography using capillary columns. The kinetic calculations were carried out with a newly developed model, which assumes a virtual volume of distribution dependent on time. IS-5-MN is rapidly (invasion half-life 4.1 min) and completely absorbed from the gastro-intestinal tract without any first pass metabolism. The maximum concentration of 480 µg/l was reached 1.2 h after oral administration of 20 mg. The substance was distributed throughout the total body water (distribution coefficient: 0.62), and was eliminated with a terminal t_1/2 of 4.1 and 4.6 h after oral and intravenous administration, respectively. Total body clearance was 115 ml/min. Thus, IS-5-MN is unlike ISDN with respect to the absence of first-pass metabolism and an 8-times longer half-life. The consequences for therapy are discussed.