Pharmacokinetics of isosorbide mononitrate.

Pharmacokinetic studies show that isosorbide mononitrate is rapidly absorbed after oral administration, reaches peak concentrations within an hour, undergoes no significant first-pass metabolism, and is virtually 100% bioavailable. The half-life is approximately 5 hours, the volume of distribution is 0.62 liter/kg, and the systemic clearance is 115 mL/min. Only 1-2% of an orally administered dose is excreted unchanged in the urine, with the remainder being eliminated as inactive metabolites. Isosorbide mononitrate follows dose-linear kinetics after single and multiple doses. Its pharmacokinetic profile is consistent and highly reproducible and is unchanged in the elderly and in patients with coronary artery disease, renal failure, or liver cirrhosis. An asymmetrical dosage regimen of isosorbide mononitrate has been shown to provide antianginal efficacy for at least 12 hours. Because asymmetrical dosing creates irregular, sawtooth-like changes in plasma concentrations and a fall below a critical threshold level during the night, tolerance does not develop.