First pass effect of pinazepam in the rabbit liver

The liver first pass effect of pinazepam in four anaesthetized rabbits was determined by measuring the concentrations of this compound and those of its metabolite N-desmethyldiazepam in the plasma from the portal and hepatic veins. Anaesthesia was induced with an i.p. injection of urethane (1.5 g/kg). Portal and hepatic veins were exposed by midline incision. Pinazepam (20 mg/kg) was orally administered in a single dose by stomach intubation. Blood was simultaneously drawn from the portal and hepatic veins of each rabbit at different intervals after dosing. Pinazepam plasma levels were significantly higher in portal than hepatic vein. While N-desmethyldiazepam concentrations were significantly higher in the hepatic than portal vein plasma. Therefore, it has been demonstrated that the rabbit liver extracts pinazepam from the blood and converts this compound into N-desmethyldiazepam.