Isosorbide 5-mononitrate and isosorbide 2-mononitrate kinetics after intravenous and oral dosing

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Abstract
Isosorbide 5-mononitrate (IS-5-MN) and isosorbide 2-mononitrate (IS-2-MN) kinetics were studied in 2 groups of young healthy subjects after 5 mg i.v. injection of both and 20 mg oral doses of IS-2-MN and 10, 15, and 20 mg of IS-5-MN. Mononitrate plasma levels were measured by GLC with capillary columns. After i.v. injection, IS-5-MN and IS-2-MN plasma levels declined biexponentially and could be described by an open 2 compartment body model. Distribution t1/2 [half life] was rapid; 8.6 min for IS-5-MN and 12.5 min for IS-2-MN. Substances were distributed throughout body water; distribution volume at steady state (Vdss) was 48 l for IS-5-MN and 55 l for IS-2-MN and elimination t1/2 was 4.15 h for IS-5-MN and 1.9 h for IS-2-MN. Total plasma clearance was 8.5 l/h for IS-5-MN and 23.2 l/h for IS-2-MN. After oral doses the mononitrates were rapidly and completely absorbed (absorption t1/2 was 2.5-5 min) from the gastrointestinal tract without first pass metabolism, i.e., absolute systemic availability was 100%. In the dose range studied, kinetics of the 2 mononitrates were linear. Compared with isosorbide dinitrate, mononitrate kinetics are different because of greater systemic availability, slower clearance and smaller Vdss.

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