Pharmacokinetics of oral L-isoidide mononitrate in rats

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.