Linked Life Data

1562288

Source:http://linkedlifedata.com/resource/pubmed/id/1562288

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1992-5-13
pubmed:abstractText
Phenobarbitone-pretreated male Sprague-Dawley rat liver microsomes were used to examine C3-hydroxylation and N-dealkylation of four clinically important benzodiazepines: diazepam (DZP), prazepam (PZP), pinazepam (PIN) and halazepam (HZP). These substrates differ only in the nature of the N-substituent of the B ring and N-desmethyldiazepam (DMD) is the N-dealkylation product in each case. C3-Hydroxylation was accordingly also studied with DMD as substrate. All monooxygenations were studied with substrates at a concentration of 10 microM, in the absence of solubilizing agents, and under conditions where the production of secondary metabolites was minimized. A 20-fold variation in the rate of C3-hydroxylation was recorded across the five substrates with HZP showing the highest rate and DMD showing the lowest rate. An almost equally large range of variation was shown for the N-dealkylation reaction, with PZP undergoing this biotransformation more than 17 times faster than DZP. Log P values (a measure of lipophilicity) for the five substrates were determined using an HPLC method and a remarkable lack of correspondence between this substrate parameter and either of the monooxygenations was noted. This suggests that multiple substrate determinants govern the relative rates of these monooxygenations. It was, however, notable that the additive rate of metabolism of these substrates by both monooxygenase routes did show an excellent correlation with substrate lipophilicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1377-80
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Comparative metabolism of clinically important precursors of N-desmethyldiazepam using phenobarbitone-pretreated rat liver microsomes.
pubmed:affiliation
Department of Medicine, University of Queensland, St Lucia, Queensland, Australia.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't