Pharmacokinetics of noreximide in the beagle dog

The psychopharmacologically active drug noreximide was administered in a crossover design to beagle dogs intravenously, and perorally in form of a solution and as capsule. The dosage forms were prepared from 14C-labeled noreximide and cold material. The total radioactivity and that of the metabolite were determined in plasma after TLC separation. The mean half-life of the parent compound is about 4.5 hours after I.V. and 9.5 hours after P.O. administration. The apparent volume of distribution is about 20 l/kg, and the total clearance about 44 l/h after I.V. and about 29 l/h after P.O. dosing. The absolute bioavailability is about 50%. The drug is completely absorbed but undergoes extensive first-pass metabolism. The main metabolite, noreximide-epoxide has an elimination half-life of about 20 hours and an apparent volume of distribution identical to that of the parent compound. The peak metabolite concentrations occur about 10 hours after dosing.