Linked Life Data

6147254

Source:http://linkedlifedata.com/resource/pubmed/id/6147254

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1984-9-28
pubmed:abstractText
The genetically controlled polymorphism causing decreased metabolism of debrisoquine is closely related to that of the metabolism of bufuralol and numerous other drugs and has important clinical consequences. A sensitive in vitro assay was developed which quantifies the production of 1'-hydroxy-bufuralol (carbinol) from bufuralol in human liver microsomes. Initial formation rates of carbinol suggested Michaelis-Menten kinetics with an apparent KM of 61 and 171 mumol l-1 and Vmax of 3.2 and 5.8 nmol mg-1 microsomal protein h-1 in two human liver samples. The Vmax in microsomes of thirty-two liver samples was 4.2 +/- 1.0 (SD) nmol carbinol mg-1 protein h-1. Metabolism of debrisoquine in vivo, as expressed by the 'metabolic ratio' of debrisoquine over 4-OH debrisoquine correlated (r = -0.65, P less than 0.01; n = 18) with carbinol production rate in microsomes in vitro. Microsomes of one individual identified as poor metabolizer of debrisoquine in vivo showed reduction of carbinol formation to 1.97 nmol mg-1 h-1. Mixing his microsomes with those of an extensive metabolizer resulted in additive formation of carbinol excluding mediation of the defect by a soluble inhibitor. These data support the concept of a primary defect in microsomal oxidation of bufuralol. The described assay offers a sensitive tool to investigate the molecular mechanism of the 'debrisoquine polymorphism'.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0014-2972
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
184-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1984
pubmed:articleTitle
Bufuralol metabolism in human liver: a sensitive probe for the debrisoquine-type polymorphism of drug oxidation.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't