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Titolo:
Small effects of valproic acid on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenic or affective disorders
Autore:
Facciola, G; Avenoso, A; Scordo, MG; Madia, AG; Ventimiglia, A; Perucca, E; Spina, E;
Indirizzi:
Univ Messina Policlin, Inst Pharmacol, I-98100 Messina, Italy Univ MessinaPoliclin Messina Italy I-98100 acol, I-98100 Messina, Italy Ctr Mental Hlth, Messina, Italy Ctr Mental Hlth Messina ItalyCtr Mental Hlth, Messina, Italy Villa Gerani Clin, Catania, Italy Villa Gerani Clin Catania ItalyVilla Gerani Clin, Catania, Italy Univ Pavia, Dept Internal Med, Clin Pharmacol Unit, I-27100 Pavia, Italy Univ Pavia Pavia Italy I-27100 Clin Pharmacol Unit, I-27100 Pavia, Italy
Titolo Testata:
THERAPEUTIC DRUG MONITORING
fascicolo: 3, volume: 21, anno: 1999,
pagine: 341 - 345
SICI:
0163-4356(199906)21:3<341:SEOVAO>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
SERUM CONCENTRATIONS; THERAPY;
Keywords:
valproic acid; clozapine; norclozapine; clozapine N-oxide; drug interaction;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Spina, E Univna,ssina Policlin, Inst Pharmacol, Via Consolare Valeria, I-98100 Messi Univ Messina Policlin Via Consolare Valeria Messina Italy I-98100
Citazione:
G. Facciola et al., "Small effects of valproic acid on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenic or affective disorders", THER DRUG M, 21(3), 1999, pp. 341-345

Abstract

Two separate studies were carried out to assess the effect of valproic acid on the steady-state plasma concentrations of clozapine and its major metabolites norclozapine and clozapine N-oxide in psychotic patients. In the first study, concentrations of clozapine and metabolites were compared between patients treated with clozapine in combination with sodium valproate (n =15) and control patients treated with clozapine alone (n = 22) and matchedfor sex, age, body weight, and antipsychotic dosage. Patients comedicated with valproate tended to have higher clozapine levels and lower norclozapine levels, but the differences did not reach statistical significance. In a subsequent study plasma concentrations of clozapine and its metabolites were determined in 6 patients with schizophrenia stabilized on clozapine therapy (200-400 mg/d) before and after treatment with sodium valproate (900-1200 mg/d) for 4 weeks. Mean plasma concentrations of clozapine and its metabolites did not change significantly throughout the study, but there was a trend for clozapine levels to be higher and for norclozapine levels to be lower after valproate. Overall, these findings suggest that valproic acid may have an inhibiting effect on the CYP1A2- or CYP3A4-mediated conversion of clozapine to norclozapine. However, the interaction is unlikely to be clinically significant.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 10:30:09