Back to Search
Start Over
Non-competitive inhibition of clomipramineN-demethylation by fluvoxamine
- Source :
- Psychopharmacology. 117:149-153
- Publication Year :
- 1995
- Publisher :
- Springer Science and Business Media LLC, 1995.
-
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-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.
- Subjects :
- Male
medicine.medical_specialty
Clomipramine
Serotonin reuptake inhibitor
Fluvoxamine
In Vitro Techniques
Pharmacology
Hydroxylation
Rats, Sprague-Dawley
Pharmacokinetics
Internal medicine
medicine
Animals
Humans
chemistry.chemical_classification
Drug interaction
Rats
Endocrinology
chemistry
Dealkylation
Depression, Chemical
Microsomes, Liver
Serotonin
Reuptake inhibitor
medicine.drug
Tricyclic
Subjects
Details
- ISSN :
- 14322072 and 00333158
- Volume :
- 117
- Database :
- OpenAIRE
- Journal :
- Psychopharmacology
- Accession number :
- edsair.doi.dedup.....e142643493fd38b36806e8b7ec7a5668