Methadone disposition following oral versus parenteral dose administration in rats during chronic treatment

A single radiolabeled dose of dl-methadone was administered by the oral, subcutaneous and intravenous routes to rats that had been chronically treated with dl-methadone. Radiolabeled compound (methadone and metabolites) was found in all organs at all time points studied after 30 minutes to 24 hours. Thin-layer chromatographic analysis showed that approximately 30-40 per cent of this compound is unchanged methadone at the 1-hour time point in the liver of rats receiving an oral or intravenous dose and in the brain of rats receiving an oral dose. Ninety-four per cent of compounds in brain is unchanged methadone at 1 hour after intravenous dose administration. Twenty-four hours following dose administration, levels of methadone within any organ are found to be similar irrespective of route of administration. The liver was found to contain the largest amounts of methadone in all animals studied with whole blood, lungs, and kidneys also containing large total amounts of methadone and metabolites. The liver and adrenals contained the highest concentration of radiolabeled compounds.