Linked Life Data

21476971

Source:http://linkedlifedata.com/resource/pubmed/id/21476971

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-7-11
pubmed:abstractText
This review focuses on stereoselectivity of human cytochrome P450 (P450 or CYP) in the area of metabolism and inhibition. A meta-analysis was performed based on the reported values regarding (1) values of the Michaelis-Menten constant (K(m)), maximal velocity (V(max)), and intrinsic clearance (V(max)/K(m)) for 45 metabolic reactions of 19 substrates and (2) inhibition constants (K(i)) for 6 inhibitors. The median (R)/(S)-enantiomer ratios of the K(m), V(max), and V(max)/K(m) values for CYP1A2, CYP2B6, CYP2C19, CYP2D6, and CYP3A4 were in the range of 0.80-1.53, whereas the median ratios of V(max), and V(max)/K(m) values for CYP2C9 were 0.43 and 0.60, respectively. In addition, the parameters for metabolic reactions (25-80%) of (R)-enantiomers of these P450s were comparable to those of (S)-enantiomers (the ratios were between 0.5 and 2), whereas 45-69% of V(max) and V(max)/K(m) values for the (R)-enantiomer in CYP2C9 were less than half of those for the (S)-enantiomer, although the kinetic behavior of the stereoselectivity depended on the metabolic reaction. There is a limited number of reports regarding stereoselective inhibition and induction in vitro. The present information gives insight into the contribution of stereoselectivity to metabolism mediated by P450s and the risk of adverse drug-drug interactions due to stereoselectivity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1875-5453
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
549-69
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Stereoselectivity of human cytochrome p450 in metabolic and inhibitory activities.
pubmed:affiliation
Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Higashi-Tamagawa Gakuen, Machida, Tokyo, Japan.
pubmed:publicationType
Journal Article, Review, Meta-Analysis