Influence of Ethanol and Gender on Methylphenidate Pharmacokinetics and Pharmacodynamics

This study explores the hypotheses that: (1) ethanol will interact with dl‐Methylphenidate (MPH) to enantioselectively elevate plasma d‐MPH, and primarily yield l‐ethylphenidate as a transesterification metabolite; (2) women will exhibit lower relative bioavailability of MPH than men; and (3) sex‐de...

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Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2007-03, Vol.81 (3), p.346-353
Main Authors: Patrick, K S, Straughn, A B, Minhinnett, R R, Yeatts, S D, Herrin, A E, DeVane, C L, Malcolm, R, Janis, G C, Markowitz, J S
Format: Article
Language:English
Subjects:
Adult
Area Under Curve
Biological and medical sciences
Biotransformation
Blood Pressure - drug effects
Body Temperature - drug effects
Central Nervous System Depressants - pharmacokinetics
Central Nervous System Depressants - pharmacology
Central Nervous System Stimulants - pharmacokinetics
Central Nervous System Stimulants - pharmacology
Cross-Over Studies
Drug Interactions
Ethanol - pharmacokinetics
Ethanol - pharmacology
Female
Heart Rate - drug effects
Humans
Male
Medical sciences
Methylphenidate - analogs & derivatives
Methylphenidate - metabolism
Methylphenidate - pharmacokinetics
Methylphenidate - pharmacology
Pharmacogenetics
Pharmacology. Drug treatments
Respiratory Mechanics - drug effects
Sex Characteristics
Stereoisomerism
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Summary:This study explores the hypotheses that: (1) ethanol will interact with dl‐Methylphenidate (MPH) to enantioselectively elevate plasma d‐MPH, and primarily yield l‐ethylphenidate as a transesterification metabolite; (2) women will exhibit lower relative bioavailability of MPH than men; and (3) sex‐dependent differences in subjective effects will exist. dl‐MPH HCl (0.3 mg/kg) was administered orally 30 min before ethanol, 30 min after ethanol (0.6 gm/kg), or without ethanol, in a randomized, normal subject three‐way crossover study of 10 men and 10 women. Pharmacokinetic parameters were compared. Subjective effects were recorded using visual analog scales. One subject was a novel poor MPH metabolizer whose data were analyzed separately. Ethanol after or before MPH significantly (P
ISSN:0009-9236
1532-6535
DOI:10.1038/sj.clpt.6100082