Linked Life Data

7753960

Source:http://linkedlifedata.com/resource/pubmed/id/7753960

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-6-22
pubmed:abstractText
The selective serotonin reuptake inhibitor fluvoxamine interferes with the metabolism of tricyclic antidepressants. The present investigation was set out to characterize these interactions in vitro using rat liver microsomes and in vivo by analysing levels of clomipramine and metabolites in sera of depressed patients treated concomitantly with fluvoxamine and clomipramine. Clomipramine was N-demethylated and hydroxylated in vitro by microsomes to N-desmethyl-clomipramine, 8-hydroxyclomipramine, and 10-hydroxyclomipramine. Kinetic analyses revealed Km values of 6.2 microM for N-demethylation and 1.2 microM for 8-hydroxylation. Fluvoxamine was a non-competitive inhibitor for N-demethylation with mean Ki value of 6 microM. In the sera of patients treated with daily doses of 150 mg clomipramine and varying doses of fluvoxamine, decrease in the formation of N-desmethylclomipramine and 8-hydroxyclomipramine were found in comparison to those in sera of patients receiving clomipramine as monotherapy. Taken together, the data give evidence that fluvoxamine is a potent non-competitive inhibitor of N-demethylation and to a minor extent of 8-hydroxylation of clomipramine. Because of the species differences in the metabolism of xenobiotics between rodents and humans, conclusions from animal studies on the clinical situation must be drawn cautiously. Nevertheless, the in vitro approach was helpful to understand drug interactions between clomipramine and fluvoxamine in psychiatric patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0033-3158
pubmed:author
pubmed:issnType
Print
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
149-53
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Non-competitive inhibition of clomipramine N-demethylation by fluvoxamine.
pubmed:affiliation
Department of Psychiatry, University of Mainz, Germany.
pubmed:publicationType
Journal Article, In Vitro