Linked Life Data

15133245

Source:http://linkedlifedata.com/resource/pubmed/id/15133245

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-5-10
pubmed:abstractText
Oxatomide is an antiallergic drug used for the treatment of diseases mediated by type I allergy. Recently, it has been reported that terfenadine and astemizole, which have antiallergic actions similar to those of oxatomide, show side effects on the cardiovascular system, such as QT prolongation, ventricular arrhythmia and cardiac arrest. This might be because concomitant drugs such as itraconazole inhibit cytochrome P450 3A4 (CYP3A4), the enzyme responsible for degradation of terfenadine and astemizole, and thus the blood concentrations of the drugs are abnormally increased. On the other hand, isoforms of P450 involved in the metabolism of oxatomide have not been clarified. Therefore, we attempted to identify these isoforms using microsome preparations of in vitro expression systems derived from a human lymphoblastoid cell line. Oxatomide was metabolized by CYP2D6-Val and CYP3A4, but not by CYP1A2, CYP2C9-Arg, CYP2C9-Cys or CYP2C19. We also examined whether oxatomide showed inhibitory effects on metabolic activity of individual P450 isozymes using model substrates for each isozyme. Oxatomide did not inhibit the metabolism of the model substrates for CYP1A2, CYP2C9-Arg, CYP2C9-Cys and CYP2C19, but inhibited the degradation of those for CYP2D6-Val and CYP3A4. It was found that oxatomide is metabolized by CYP2D6 and CYP3A4 in human liver microsomes, and simultaneously acts as an inhibitor for these isoforms, responsible for the metabolism of the drug itself.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0918-6158
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
684-90
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Identification of human p450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its inhibitory effect on enzyme activity.
pubmed:affiliation
Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
pubmed:publicationType
Journal Article, Comparative Study