Linked Life Data

17651723

Source:http://linkedlifedata.com/resource/pubmed/id/17651723

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-10-8
pubmed:abstractText
The aim of this report is to study the circadian rhythm of cytochrome P4502E1 (CYP2E1) and its effect on the disposition kinetics of chlorzoxazone in male Wistar rats. The rats were housed under a 12-h light/dark cycle (lights from 9:00 to 21:00) with food and water ad libitum for 3 months. It was found that the expression of microsomal CYP2E1 mRNA in the liver during the dark phase was significantly lower than during the light phase, whereas the content of CYP2E1 protein and its hydroxylation activity were significantly higher. Therefore, chlorzoxazone 20 mg/kg was intravenously administered at 12:00 (light phase group) or 24:00 (dark phase group) to determine the effect on the disposition kinetics. The value of the area under the plasma concentration-time curve from 0 to 8 h (AUC(0-8 h)) of chlorzoxazone showed no significant difference between the two groups. However, the value of chlorzoxazone half-life in plasma of the light phase group was significant longer than the dark phase group. The AUC(0-8 h) of 6-hydroxychlorzoxazone, a metabolite formed from chlorzoxazone mainly by CYP2E1, was significantly higher in the dark phase than in the light phase. In conclusion, microsomal CYP2E1 shows a substantial circadian variation in rats, and this was associated with a decrease of chlorzoxazone half life, and an increase of 6-hydroxychlorzoxazone production. Therefore, the temporal variations of therapeutic response and toxicological effects may have to be taken into consideration for other xenobiotics that are predominantly metabolized by CYP2E1, particularly those with a short half-life.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
574
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
71-6
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Circadian rhythm of cytochrome P4502E1 and its effect on disposition kinetics of chlorzoxazone in rats.
pubmed:affiliation
Department of Medicinal Informatics, Division of Cardiovascular Medicine, Graduate School of Medical Science, Kanazawa University, Japan.
pubmed:publicationType
Journal Article