Linked Life Data

7678683

Source:http://linkedlifedata.com/resource/pubmed/id/7678683

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1993-2-25
pubmed:abstractText
Mexiletine, a class Ib antiarrhythmic drug, is used clinically as a racemic mixture of two enantiomers. Aromatic and aliphatic hydroxylation are the two major metabolic steps. In the liver, this metabolism is catalyzed by the cytochrome P450IID6, an isoenzyme of cytochrome P450 due to genetic polymorphism in humans. In the present study, the metabolism of the two stereoisomers was compared in vitro in human liver microsomes. Parahydroxylation (aromatic hydroxylation) is favored for S(+)-mexiletine with a mean intrinsic clearance higher than for R(-)-mexiletine. The R(-) enantiomer exhibits a threefold higher mean Vmax value for aliphatic hydroxylation than S(+)-mexiletine. We showed that (i) the high-affinity component of dextrometorphan O-demethylation was competitively inhibited by R(-)- and S(+)-mexiletine and that (ii) hydroxylations of the two enantiomers were very strongly competitively inhibited by quinidine. Hydroxylation reactions of mexiletine exhibit stereoselectivity in vitro in human liver microsomes and are catalyzed by P450IID6.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0160-2446
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
77-83
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Stereoselective hydroxylation of mexiletine in human liver microsomes: implication of P450IID6--a preliminary report.
pubmed:affiliation
Secteur Toxicologie du Laboratoire de Biochimie, Hôpital Calmette, CHRU de Lille, France.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't