METABOLISM AND EXCRETION OF TRITIATED DEXTROMETHORPHAN BY THE RAT

¹ Research and Development Division, Smith Kline & French Laboratories, Philadelphia, Pennsylvania

After administration of a single p.o. or i.p. dose of 10 mg/kg of dextromethorphan-H³ in male Sprague-Dawley rats, 54 to 57% of the administered radioactivity was excreted in urine and feces within 3 to 4 days, and about 75% of that during the first 24 hr. About 65% of the total radioactivity excreted within 4 days was recovered from feces, indicating that this is the major route of excretion of dextromethorphan and its metabolites. Similar results followed administration of a single dose of dextromethorphan-H³ in rats pretreated for 7 days with unlabeled drug, indicating that multiple doses of this compound are excreted to the same extent as a single dose. From 68 to 84% of the administered radioactivity was excreted in bile within 24 hr after administration of a single i.p. dose of dextromethorphan-H³ in rats with chronic bile duct cannulation. Only 3% of dextromethorphan-H³ was excreted unmetabolized in urine within 24 hr; none was excreted unmetabolized in bile. Major metabohites of dextromethorphan-H³ in bile and urine were d-3-hydroxy-N-methyl-morphinan and its sulfate and glucuronide conjugates; d-3-hydroxymorphinan and its glucuronide and sulfate conjugates were minor metabolites.