Linked Life Data

10653206

Source:http://linkedlifedata.com/resource/pubmed/id/10653206

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-3-15
pubmed:abstractText
Administration of fluvoxamine to patients receiving clozapine therapy may increase the steady-state serum concentrations of clozapine by a factor of 5 to 10. The authors undertook in vitro studies to disclose the mechanism behind this clinically important interaction. In a human liver microsome preparation, fluvoxamine showed a concentration-dependent inhibition of clozapine N-demethylation. Fluvoxamine was much less effective as an inhibitor of clozapine N-oxidation. Fluvoxamine also inhibited in a concentration-dependent manner the activity of all five cytochrome P450 (CYP) isoforms previously determined to be capable of catalyzing the demethylation of clozapine. Fluvoxamine inhibited CYP1A2 and 2C19 with the highest affinities (Ki values of 0.041 and 0.087 microM, respectively). The Ki values for CYP2C9 and 2D6 were 2.2 and 4.9 microM, respectively, whereas the Ki for CY3A4 was 24 microM. Assuming a hepatic tissue concentration of fluvoxamine in the range of 4 to 7 microM under therapeutic conditions, a clinically significant inhibition of all but CYP3A4 is expected in relation to clozapine N-demethylation. No significant effect of fluvoxamine on clozapine N-oxidation is to be expected under therapeutic conditions. Because of the large interindividual variability of the quantity of the various CYP isoforms in liver tissue, it is not possible to predict the fluvoxamine-induced increase in the plasma concentration of clozapine of an individual patient.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0271-0749
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35-42
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Fluvoxamine-Clozapine drug interaction: inhibition in vitro of five cytochrome P450 isoforms involved in clozapine metabolism.
pubmed:affiliation
Institute for Basic Psychiatric Research, Department of Biological Psychiatry, Psychiatric Hospital in Aarhus, Risskov, Denmark.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't