Pharmacokinetics of stereomeric 1,4:3,6-dianhydrohexitol mononitrates in rats (original) (raw)

Pharmaceutical research, 1993

Abstract

The pharmacokinetics and urinary recoveries of four isomeric mononitrates, L-isoidide mononitrate (L-IIMN), isosorbide-2-mononitrate (IS-2-MN), isomannide mononitrate (IMMN), and isosorbide-5-mononitrate (IS-5-MN), were investigated at an intravenous dose of 2 mg/kg in rats. All four compounds exhibited monoexponential kinetics at this dose. The volumes of distribution were similar for all four isomers and were estimated at about 1.0 liter/kg. The systemic clearances of L-IIMN, IMMN, IS-2-MN, and IS-5-MN were 65.1 +/- 13.0, 32.7 +/- 12.0, 11.0 +/- 2.3, and 8.23 +/- 1.82 ml/min/kg, respectively (P < 0.05, all pairwise comparisons). Free mononitrate in the urine accounted for 0.306 to 4.56% of the administered dose, while the recovery in conjugated forms (after glusulase hydrolysis) accounted for 42.8% of the IMMN dose and 7.70 to 14.5% of the dose of the remaining three isomers. The dose-dependent pharmacokinetics of three of the mononitrates were explored at selected higher doses...

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