Linked Life Data

7439248

Source:http://linkedlifedata.com/resource/pubmed/id/7439248

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1981-2-24
pubmed:abstractText
Ethanol may enhance the sedative effect of benzodiazepines leading to greater psychomotor impairment, but the mechanism is not clear. The present study was carried out to determine the effect of acute ethanol ingestion on the disposition and elimination of chlordiazepoxide (Librium), a widely used benzodiazepine. Five healthy, 22-39-year-old, male volunteers ingested ethanol 0.8 g/kg as 25% in orange juice 1 h before chlordiazepoxide 0.6 mg/kg was injected intravenously. To maintain plasma ethanol concentrations of 50-150 mg!100 ml for 32 h additional ethanol 0.5 g/kg was given orally every 5 h. Plasma clearance of chlordiazepoxide fell from 26.6 +/- 2.6 ml/min (mean +/- SD) without ethanol to 16.6 +/- 3.1 ml/min (P less than 0.05) after ethanol. There was no change in the volume of distribution and therefore the elimination half-life was prolonged from 7.1 +/- 1.9 h to 11.8 +/- 6.0 h (P less than 0.05) after ethanol. Ethanol also lowered the plasma binding of chlordiazepoxide from 94.7 +/- 0.6% to 93.4 +/- 1.3% (P less than 0.05). The plasma clearance of unbound chlordiazepoxide fell from 468 +/- 51 ml/min to 264 +/- 98 ml/min (P less than 0.05) after ethanol. The plasma level of the metabolite desmethylchlordiazepoxide was higher and its elimination slower after ethanol. Thus using a pharmacokinetic approach this study has demonstrated that short-term ethanol ingestion in moderate doses impairs the elimination of chlordiazepoxide and accounts, at least partly, for the greater sedation that results when ethanol is taken concomitantly.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0031-6970
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
275-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1980
pubmed:articleTitle
Short-term ethanol administration impairs the elimination of chlordiazepoxide (Librium) in man.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.