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Research ArticleArticle

Ethylphenidate Formation in Human Subjects after the Administration of a Single Dose of Methylphenidate and Ethanol

John S. Markowitz, C. Lindsay DeVane, David W. Boulton, Ziad Nahas, S. Craig Risch, Fran Diamond and Kennerly S. Patrick
Drug Metabolism and Disposition June 2000, 28 (6) 620-624;
John S. Markowitz
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C. Lindsay DeVane
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David W. Boulton
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Ziad Nahas
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S. Craig Risch
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Fran Diamond
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Kennerly S. Patrick
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Abstract

Ethylphenidate was recently reported as a novel drug metabolite in two overdose fatalities where there was evidence of methylphenidate and ethanol coingestion. This study explores the pharmacokinetics of ethylphenidate relative to methylphenidate and the major metabolite ritalinic acid, in six healthy subjects who received methylphenidate and ethanol under controlled conditions. Subjects (three males, three females) received a single oral dose of methylphenidate (20 mg; two 10-mg tablets) followed by consumption of ethanol (0.6 g/kg) 30 min later. Methylphenidate, ritalinic acid, and ethylphenidate were quantified using liquid chromatography-tandem mass spectrometry. Ethylphenidate was detectable in the plasma and urine of all subjects after 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 correlation was observed between the area under the concentration versus time curve of methylphenidate and that of ethylphenidate. In view of the known dopaminergic activity of racemic ethylphenidate, it remains possible that under certain circumstances of higher level dosing, e.g., in the abuse of methylphenidate and ethanol, the metabolite ethylphenidate may contribute to drug effects.

Footnotes

  • Send reprint requests to: John S. Markowitz, Pharm.D., Institute of Psychiatry, Rm 338N, Medical University of South Carolina, 67 President St., P.O. Box 250861, Charleston, SC 29425. E-mail:markowij{at}musc.edu

  • Abbreviations used are::
    ADHD
    attention-deficit hyperactivity disorder
    CNS
    central nervous system
    LC
    liquid chromatography
    MS
    mass spectrometry
    AUC
    area under the concentration versus time curve
    t1/2
    terminal phase half-life
    • Received December 3, 1999.
    • Accepted February 1, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 28 (6)
Drug Metabolism and Disposition
Vol. 28, Issue 6
1 Jun 2000
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Research ArticleArticle

Ethylphenidate Formation in Human Subjects after the Administration of a Single Dose of Methylphenidate and Ethanol

John S. Markowitz, C. Lindsay DeVane, David W. Boulton, Ziad Nahas, S. Craig Risch, Fran Diamond and Kennerly S. Patrick
Drug Metabolism and Disposition June 1, 2000, 28 (6) 620-624;

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Research ArticleArticle

Ethylphenidate Formation in Human Subjects after the Administration of a Single Dose of Methylphenidate and Ethanol

John S. Markowitz, C. Lindsay DeVane, David W. Boulton, Ziad Nahas, S. Craig Risch, Fran Diamond and Kennerly S. Patrick
Drug Metabolism and Disposition June 1, 2000, 28 (6) 620-624;
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