Linked Life Data

7826796

Source:http://linkedlifedata.com/resource/pubmed/id/7826796

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1995-2-21
pubmed:abstractText
Distribution volumes and metabolism determine the pharmacokinetics of midazolam. Cytochrome P450 3A4 has been considered a significant enzyme in its metabolism. Using heterologously expressed cytochrome P450 enzymes, we have confirmed the additional involvement of cytochromes P450 3A3 and 3A5 in the hydroxylation of the midazolam. Whereas cytochrome P450 3A3 metabolized midazolam to the same extent as cytochrome P450 3A4, cytochrome P450 3A5 increased its metabolism by a factor of 2.7. The relationship of alpha- to 4-hydroxylation of midazolam was approximately 1.3 for cytochromes P450 3A3 and 3A4, and approximately 8.8 for 3A5. The primary location of cytochromes P450 3A3 and 3A4 is the liver in contrast with cytochrome P450 3A5, which occurs predominantly in the kidney. Therefore, further in vivo study is required to prove conclusively that enzymes in the kidney are involved in the metabolism of midazolam. Nitrendipine itself is metabolized by cytochrome P450 3A enzymes and this was shown to inhibit human liver microsomal hydroxylation of midazolam and preferentially alpha-hydroxylation by about 77%. 4-Hydroxylation was inhibited to 32% of control by nitrendipine. In contrast with inhibition of 4-hydroxylation, alpha-hydroxylation would appear to be competitively inhibited. These findings may be relevant to drug interactions in combined therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0007-0912
pubmed:author
pubmed:issnType
Print
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
658-61
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Midazolam is metabolized by at least three different cytochrome P450 enzymes.
pubmed:affiliation
Department of Anaesthesia, University of Heidelberg, Germany.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't