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Titolo:
PHARMACOKINETIC INTERACTIONS OF CLOZAPINE WITH SELECTIVE SEROTONIN REUPTAKE INHIBITORS - DIFFERENTIAL-EFFECTS OF FLUVOXAMINE AND PAROXETINEIN A PROSPECTIVE-STUDY
Autore:
WETZEL H; ANGHELESCU I; SZEGEDI A; WIESNER J; WEIGMANN H; HARTTER S; HIEMKE C;
Indirizzi:
UNIV MAINZ,DEPT PSYCHIAT,UNTERE ZAHLBACHER STR 8 D-55131 MAINZ GERMANY
Titolo Testata:
Journal of clinical psychopharmacology
fascicolo: 1, volume: 18, anno: 1998,
pagine: 2 - 9
SICI:
0271-0749(1998)18:1<2:PIOCWS>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
DRUG-INTERACTIONS; IN-VITRO; N-DESMETHYLCLOZAPINE; MAJOR METABOLITES; SERUM; HYDROXYLATION; PHARMACODYNAMICS; ANTIDEPRESSANTS; FLUOXETINE; INITIATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
H. Wetzel et al., "PHARMACOKINETIC INTERACTIONS OF CLOZAPINE WITH SELECTIVE SEROTONIN REUPTAKE INHIBITORS - DIFFERENTIAL-EFFECTS OF FLUVOXAMINE AND PAROXETINEIN A PROSPECTIVE-STUDY", Journal of clinical psychopharmacology, 18(1), 1998, pp. 2-9

Abstract

Pharmacokinetic interactions of clozapine and its metabolites N-desmethylclozapine and clozapine N-oxide with the selective serotonin reuptake inhibitors (SSRIs) fluvoxamine and paroxetine were investigated ina prospective study in schizophrenic patients under steady-state conditions. Thirty patients were treated with clozapine at a target dose of 2.5 to 3.0 mg/kg of body weight. After gradual dose escalation, serum concentrations of clozapine and two metabolites were determined twice at 7-day intervals after steady-state conditions had been reached. Then, fluvoxamine (50 mg/day) or paroxetine (20 mg/day) was added in 16and 14 patients, respectively. Serum concentrations of clozapine and its metabolites were measured after 1, 7, and 14 days of coadministration with the SSRI. Mean trough concentrations of steady-state serum concentrations of clozapine, N-desmethylclozapine, and clozapine N-oxidewere markedly elevated under fluvoxamine by about threefold of baseline concentrations whereas paroxetine induced only minor, nonsignificant changes. Estimation of the mean elimination half-life of clozapine 2weeks after start of fluvoxamine comedication revealed an increase from 17 hours to about 50 hours whereas there was no change under paroxetine coadministration. The N-desmethylclozapine/clozapine ratio did not change significantly with either SSRI. Under monotherapy, clozapine mean serum concentrations in smokers were significantly lower by 32% compared with nonsmokers. Similarly, N-demethylation ratios were about 20 to 50% higher in smokers. Thus, in all patients, fluvoxamine induced relevant increases in serum concentrations of clozapine and its metabolites, probably by the inhibition of enzymes catalyzing the degradation of clozapine and N-desmethylclozapine, whereas paroxetine, at a usual clinically effective dosage of 20 mg/day, did not cause significant pharmacokinetic interactions.

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Documento generato il 25/01/20 alle ore 18:30:19