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.