Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and ethanol

Ethylphenidate was recently reported as a novel drug metabolite in two over dose fatalities where there was evidence of methylphenidate and ethanol coi ngestion. This study explores the pharmacokinetics of ethylphenidate relati ve to methylphenidate and the major metabolite ritalinic acid, in six healt hy subjects who received methylphenidate and ethanol under controlled condi tions. Subjects (three males, three females) received a single oral dose of methylphenidate (20 mg; two 10-mg tablets) followed by consumption of etha nol (0.6 g/kg) 30 min later. Methylphenidate, ritalinic acid, and ethylphen idate were quantified using liquid chromatography-tandem mass spectrometry. Ethylphenidate was detectable in the plasma and urine of all subjects afte r ethanol ingestion. The mean (+/-S.D.) area under the concentration versus time curve for ethylphenidate was 1.2 +/- 0.7 ng/ml/h, representing 2.3 +/ - 1.3% that of methylphenidate (48 +/- 12 ng/ml/h). A significant correlati on was observed between the area under the concentration versus time curve of methylphenidate and that of ethylphenidate. In view of the known dopamin ergic activity of racemic ethylphenidate, it remains possible that under ce rtain circumstances of higher level dosing, e.g., in the abuse of methylphe nidate and ethanol, the metabolite ethylphenidate may contribute to drug ef fects.