Linked Life Data

8961170

Source:http://linkedlifedata.com/resource/pubmed/id/8961170

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1997-3-13
pubmed:abstractText
We have examined the 4-hydroxylation of bunitrolol in rabbit and rat liver microsomes. Significant species differences (rabbit < rat of both sexes) and sex (male > female of both species) were observed in the formation of 4-hydroxybunitrolol from racemic bunitrolol (10 microM). The 4-hydroxylation of bunitrolol racemate and enantiomers showed biphasic kinetics, a low-Km system and a high-Km system, in liver microsomes from rabbits of both sexes. There were significant differences in Km and Vmax values [(+) > (-)] for 4-hydroxylations of (+)-bunitrolol and (-)-bunitrolol in the low-K(m) system. Furthermore, the rate of clearance (Vmax/Km) was 20- to 200-fold for the low-Km system compared with the high-Km system, indicating that enzymes in the low-Km system play a major part in the rabbit liver microsomal bunitrolol metabolism. Inhibition studies using cytochrome P450 inhibitors such as quinidine, quinine, and alpha-naphthoflavone or polyclonal antibodies raised against rat P450-2D and -1A enzymes did not make clear which P450 enzymes are involved in bunitrolol 4-hydroxylation in rabbit liver microsomes. The 4-hydroxylase activity of (+)-bunitrolol was slightly higher than that of (-)-bunitrolol in separated incubations containing male rabbit liver microsomes and an enantiomer concentration of 10 microM. However, the 4-hydroxylation of (+)-bunitrolol (10 microM) was markedly suppressed in the presence of its antipode (10 microM), whereas (-)-bunitrolol 4-hydroxylation was not affected by the presence of its antipode, resulting in a change of the stereoselectivity from (+) > (-) for enantiomer to (+) < (-) for racemate. The difference in the Michaelis constants in the low-Km system, where the Km value of (-)-bunitrolol is one-eighth that of (+)-bunitrolol, is thought to cause the change in the stereoselectivity in rabbit liver microsome-mediated bunitrolol 4-hydroxylation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3573
pubmed:author
pubmed:issnType
Print
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1185-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
In-vitro metabolic interaction of bunitrolol enantiomers in rabbit liver microsomes.
pubmed:affiliation
Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't