DEXTROMETHORPHAN - RADIOIMMUNOASSAY AND PHARMACOKINETICS IN DOG

1 January 1978

journal article
research article

Vol. 22 (2) , 243-255

Abstract

A specific radioimmunoassay (RIA) for the determination of the non-narcotic antitussive agent, dextromethorphan (DM) in plasma and urine was developed using an antiserum to DM obtained from rabbits following immunization with an albumin conjugate of (+)-3-methoxymorphinan-17-succinyloxyethyl. Specificity of the RIA was achieved by selective extraction of DM from its known metabolites into hexane at pH 6.5 with 86% recovery. Employing 3H-labeled-DM as the radioligand, the RIA had a limit of sensitivity of about 4 ng/ml of plasma using a 0.5 ml sample. Following i.v. administration of 2 mg/kg of DM to 2 dogs, the plasma levels of intact DM declined biexponentially; the terminal exponential phase having a half-life of 2.5-3.9 h. The volume of distribution of the central compartment ranged from 5-6.4 l/kg while the metabolic clearance rate ranged from 2.5-2.6 l/h per kg. Oral administration of 10 mg/kg of DM in gelatin capsule resulted in peak plasma levels of 50 and 92 ng/ml at 2 h post-drug. Following both routes of administration, less than 3.5% of the dose was excreted in the urine as intact DM, indicating almost complete biotransformation and/or alternate routes of excretion. In 1 human subject who received 0.5 mg/kg of DM orally in a syrup, the plasma levels were less than 1 ng/ml.

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