Linked Life Data

8971140

Source:http://linkedlifedata.com/resource/pubmed/id/8971140

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1997-3-28
pubmed:abstractText
Chloral hydrate (CH) and its metabolites, trichloroacetate (TCA) and dichloroacetate (DCA), have been shown to induce liver tumors in male B6C3F1 mice. The pharmacokinetics of CH and its metabolites play an important role in its toxicity. This study was designed to characterize the kinetics of CH metabolism, and the formation and elimination of TCA, DCA, trichloroethanol (TCOH), and trichloroethanol glucuronide (TCOG) in male B6C3F1 mice. Mice were dosed with 67.8, 678, and 2034 micromol/kg of CH through the tail vein. At selected time points, mice were killed, and blood and liver samples were collected. Samples were assayed by GC for CH, TCOH, TCOG, TCA, and DCA concentrations. After intravenous administration, CH rapidly disappeared from blood with a terminal half-life ranging from 5 to 24 min. Systemic clearance decreased from 36.0 to 7.6 liters/kg-hr with increasing CH dose, demonstrating dose-dependent pharmacokinetics. TCOH, TCOG, TCA, and DCA were detected over the study period. Formation and metabolism of CH metabolites seemed to be dose-dependent. The terminal half-lives of TCOH and TCOG were similar, ranging from 0.2 to 0.7 hr. TCA and DCA were formed rapidly from the metabolism of CH and cleared slowly from systemic circulation. The area under the blood concentration-time curve for DCA was 10-20% of that for TCA. Both TCA and DCA were slowly eliminated from systemic circulation. The concentration-time profile of DCA seemed to be driven by the blood concentration of TCA, suggesting the possibility of DCA formation from TCA metabolism.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1340-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Pharmacokinetic analysis of chloral hydrate and its metabolism in B6C3F1 mice.
pubmed:affiliation
Geo-Centers, Inc.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.