Linked Life Data

2039681

Source:http://linkedlifedata.com/resource/pubmed/id/2039681

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1991-7-8
pubmed:abstractText
Inhibition of the metabolism of (S)-warfarin, the more pharmacologically active enantiomer of the racemic drug, by (R)-warfarin was investigated in microsomes obtained from three human livers. In each case the production of both (S)-6- and (S)-7-hydroxywarfarin was found to be competitively inhibited by (R)-warfarin. The KiS for inhibition of (S)-6- and (S)-7-hydroxylation by (R)-warfarin ranged from 7.0 to 8.4 microM and from 6.0 to 6.9 microM, respectively, while the KmS for the 6- and 7-hydroxylation of (S)-warfarin ranged from 3.6 to 3.8 microM and from 3.3 to 3.9 microM, respectively. In contrast, except for the 4'-hydroxylation pathway (S)-warfarin was found to be a weak inhibitor of the metabolism of (R)-warfarin. Possible implications of these findings include the following: (1) the kinetic parameters defining the interactions of two enantiomers of a racemic drug with the cytochrome P-450s or other macromolecular systems in the living organism can only be properly defined from experiments with the pure enantiomers, (2) an enantiomer of a racemic drug may contribute significantly to biological effect not by its inherent activity but by altering the pharmacokinetics of the eutomer, and (3) enantiomeric interactions are not easily detected unless directly sought and may be relatively common.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0899-0042
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
24-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Metabolic enantiomeric interactions: the inhibition of human (S)-warfarin-7-hydroxylase by (R)-warfarin.
pubmed:affiliation
Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle 98195.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.