Pharmacokinetics of oral L-isoidide mononitrate in rats

✍ Scribed by Tsang-Bin Tzeng; Ho-Leung Fung

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 290 KB
• Volume: 14
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510140705

✦ Synopsis

L-isoidide mononitrate (L-IIMN) is the most potent mononitrate vasodilator described so far in the literature. Since other mononitrates, such as isosorbide-Smononitrate 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-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 L-3.6 min (mean L-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 L-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.