Isosorbide 5-mononitrate and isosorbide 2-mononitrate kinetics after intravenous and oral dosing.
Isosorbide 5-mononitrate (IS-5-MN) and isosorbide 2-mononitrate (IS-2-MN) kinetics were studied in two groups of young healthy subjects after intravenous injection of 5 mg of both and after oral doses of 20 mg 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 intravenous injection, IS-5-MN and IS-2-MN plasma levels declined biexponentially and could be described by an open two-compartment body model. Distribution t 1/2 was rapid; 8.6 min for IS-5-MN and 12.5 min for IS-2-MN. Substances were distributed throughout body water; volume of distribution at steady state (Vd ss) was 48 l for IS-5-MN and 55 l for IS-2-MN and elimination t 1/2 was 4.15 hr for IS-5-MN and 1.9 hr for IS-2-MN. Total plasma clearance was 8.5 l/hr for IS-5-MN and 23.2 l/hr for IS-2-MN. After oral doses the mononitrates were rapidly and completely absorbed (absorption t 1/2 ranged from 2.5 to 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 two mononitrates were linear. Compared with isosorbide dinitrate, mononitrate kinetics are different because of greater systemic availability, slower clearance, and smaller Vd ss.
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D005260:Female; D006207:Half-Life; D006801:Humans; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D007700:Kinetics; D008297:Male
C030398:isosorbide-2-mononitrate; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate