title: Pharmacokinetics of oral L-isoidide mononitrate in rats.
abstract: L-isoidide mononitrate (L-IIMN) is the most potent mononitrate vasodilator described so far in the literature. Since other mononitrates, such as isosorbide-5-mononitrate and isosorbide-2-mononitrate, have been shown not to be subject to first-pass metabolism, we examined the pharmacokinetics of L-IIMN after oral administration to determine whether this compound also exhibited this behavior. An oral dose of 2 mg kg-1 L-IIMN dissolved in normal saline was given to seven rats. Absorption of L-IIMN after dosing was rapid with an apparent absorption half-life of 9.5 +/- 3.6 min (mean +/- SD). Plasma L-IIMN concentrations peaked between 5 and 20 min after dosing and declined thereafter in an apparently monoexponential manner. The average elimination half-life was 11.9 +/- 1.7 min (mean +/- SD). Oral bioavailability was estimated to be about 50%. Thus, unlike the other mononitrates so far examined in the literature, L-IIMN exhibits incomplete bioavailability. This pharmacokinetic behavior, however, is consistent with its faster systemic clearance compared to other organic mononitrates.
authors.affiliation: Department of Pharmaceutics, State University of New York at Buffalo 14260.
authors.forename: T B
authors.initials: TB
authors.lastname: Tzeng
authors.forename: H L
authors.initials: HL
authors.lastname: Fung
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009566:Nitrates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013402:Sugar Alcohols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014665:Vasodilator Agents / Q000493:pharmacokinetics*
chemical_list: D009566:Nitrates; D013402:Sugar Alcohols; D014665:Vasodilator Agents; C084745:isoidide mononitrate