Levorphanol:radioimmunoassay and plasma concentration profiles in dog and man

A specific radioimmunoassay (RIA) procedure has been developed for the determination of the narcotic analgesic, levorphanol, in plasma using a rabbit antiserum to an albumin conjugate of (-)-3-hydroxy-N-carboxymethylmorphinan. Assay specificity was achieved by chromatogrphic isolation of levorphanol from plasma extracts on Sephadex LH-20 prior to analysis. The method has a limit of sensitivity of about 0.5 ng/ml of levorphanol using a 0.1 ml sample of plasma. Steady-state plasma concentrations of levorphanol have been determined for the first time in two cancer patients receiving chronic therapeutic doses of the drug. The plasma concentration-time profile for levorphanol following i.v. administration of 2 mg/kg to a dog declined biexponentially and the terminal elimination phase had a half-life of 2.4 hr. When another dog received orally 7 mg/kg of the drug in aqueous solution, the normalized area under the plasma concentration-time curve of intact levorphanol was less than 2% of the are observed after i.v. administration and suggests extensive "first-pass" metabolism of the drug in the dog.