COCAINE METABOLISM AND URINARY-EXCRETION AFTER DIFFERENT ROUTES OF ADMINISTRATION

Cocaine abusers frequently self-administer cocaine by different routes of administration. A controlled-dosing study was performed to assess the effect of different routes of administration on the excretion prof ile of cocaine and metabolites in urine. Single bioequivalent doses of cocaine were administered by the intravenous, intranasal, and smoked routes to six human subjects. Urine specimens were collected for 3 day s after drug administration and were analyzed for cocaine, metabolites , and anhydoecogonine methyl ester, the thermal degradation product of cocaine, by gas chromatography-mass spectrometry. Cocaine was rapidly absorbed, metabolized, and excreted in urine. Peak cocaine concentrat ions were generally present in the first specimen collected; thereafte r, concentrations declined quickly and were usually below the limit of detection (approximately 1 ng/ml) within 24 hours. The metabolite ben zoylecgonine was present in the highest concentration and represented approximately 39%, 30%, and 16%, of the administered dose by the intra venous, intranasal, and smoked routes, respectively. Combined amounts of ecgonine methyl eater and six minor metabolites (norcocaine, benzoy lnorecgonine, m-hydroxycocaine, p-hydroxycocaine, m-hydroxybenzoylecgo nine, and p-hydroxybenzoylecgonine) accounted for approximately 18%, 1 5%, and 8% of the administered dose by the intravenous, intranasal, an d smoked routes, respectively. Anhydroecgonine methyl ester was presen t in trace amounts (0.02% dose) in specimens collected after smoked co caine administration. Because many of these metabolites exhibit pharma cologic activity, their presence in urine may indicate that they play complex biologic roles in the overall activity of cocaine.