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Titolo:
NONCOMPETITIVE INHIBITION OF CLOMIPRAMINE N-DEMETHYLATION BY FLUVOXAMINE
Autore:
HARTTER S; ARAND M; OESCH F; HIEMKE C;
Indirizzi:
UNIV MAINZ,DEPT PSYCHIAT,UNTERE ZAHLBACHER STR 8 D-55101 MAINZ GERMANY UNIV MAINZ,DEPT PSYCHIAT D-55101 MAINZ GERMANY UNIV MAINZ,INST TOXICOL D-55101 MAINZ GERMANY
Titolo Testata:
Psychopharmacology
fascicolo: 2, volume: 117, anno: 1995,
pagine: 149 - 153
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; IMIPRAMINE; SEROTONIN; BINDING; PLASMA;
Keywords:
FLUVOXAMINE; CLOMIPRAMINE; DRUG INTERACTIONS; N-DEMETHYLATION; HYDROXYLATION; LIVER MICROSOMES; MAJOR DEPRESSION; TRICYLIC ANTIDEPRESSANTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Physical, Chemical & Earth Sciences
Physical, Chemical & Earth Sciences
Physical, Chemical & Earth Sciences
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
18
Recensione:
Indirizzi per estratti:
Citazione:
S. Hartter et al., "NONCOMPETITIVE INHIBITION OF CLOMIPRAMINE N-DEMETHYLATION BY FLUVOXAMINE", Psychopharmacology, 117(2), 1995, pp. 149-153

Abstract

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-desmethylclomipramine, 8-hydroxyclomipramine, and 10-hydroxyclomipramine. Kinetic analyses revealed K-m values of 6.2 mu M for N-demethylation and 1.2 mu M for 8-hydroxylation. Fluvoxamine was a non-competitive inhibitor for N-demethylation with mean K-i value of 6 mu M. In the sera of patients treated with daily doses of 150 mg clomipramine and varying doses of fluvoxamine, decreasein the formation of N-desmethylclomipramine and 8-hydroxyclomipraminewere 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 andto 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.

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Documento generato il 25/01/20 alle ore 09:19:34