Linked Life Data

17339864

Source:http://linkedlifedata.com/resource/pubmed/id/17339864

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-3-6
pubmed:abstractText
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<0.0001) elevated the geometric mean for the maximum d-MPH plasma concentration (C(max) (+/-SD)) from 15.3 (3.37) ng/ml to 21.5 (6.81) and 21.4 (4.86), respectively, and raised the corresponding geometric mean for the area under the concentration-time curve values from 82.9 (21.7) ng ml/h to 105.2 (23.5) and 102.9 (19.2). l-MPH was present in plasma only at 1-3% of the concentration of d-MPH, except in the poor metabolizer where l-MPH exceeded that of d-MPH. The metabolite l-ethylphenidate frequently exceeded 1 ng/ml in plasma, whereas d-ethylphenidate was detected only in low pg/ml concentrations. Women reported a significantly greater stimulant effect than men when questioned "Do you feel any drug effect?" (P<0.05), in spite of lower mean plasma d-MPH area under the response-time curves in women. Ethanol elevates plasma d-MPH C(max) and area under the concentration-time curve by approximately 40% and 25%, respectively. If the poor metabolizer of MPH proves to be a distinct phenotype, determining the genetic mechanism may be of value for individualizing drug therapy. The more pronounced stimulant effects experienced by women have sex-based abuse liability implications.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0009-9236
pubmed:author
pubmed:issnType
Print
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
346-53
pubmed:dateRevised
2011-10-6
pubmed:meshHeading
pubmed-meshheading:17339864-Adult, pubmed-meshheading:17339864-Area Under Curve, pubmed-meshheading:17339864-Biotransformation, pubmed-meshheading:17339864-Blood Pressure, pubmed-meshheading:17339864-Body Temperature, pubmed-meshheading:17339864-Central Nervous System Depressants, pubmed-meshheading:17339864-Central Nervous System Stimulants, pubmed-meshheading:17339864-Cross-Over Studies, pubmed-meshheading:17339864-Drug Interactions, pubmed-meshheading:17339864-Ethanol, pubmed-meshheading:17339864-Female, pubmed-meshheading:17339864-Heart Rate, pubmed-meshheading:17339864-Humans, pubmed-meshheading:17339864-Male, pubmed-meshheading:17339864-Methylphenidate, pubmed-meshheading:17339864-Pharmacogenetics, pubmed-meshheading:17339864-Respiratory Mechanics, pubmed-meshheading:17339864-Sex Characteristics, pubmed-meshheading:17339864-Stereoisomerism
pubmed:year
2007
pubmed:articleTitle
Influence of ethanol and gender on methylphenidate pharmacokinetics and pharmacodynamics.
pubmed:affiliation
Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA. patrickk@musc.edu
pubmed:publicationType
Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural