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Titolo:
Pharmacokinetic drug interaction potential of risperidone with cytochrome P450 isozymes as assessed by the dextromethorphan, the caffeine, and the mephenytoin test
Autore:
Eap, CB; Bondolfi, G; Zullino, D; Bryois, C; Fuciec, M; Savary, L; Jonzier-Perey, M; Baumann, P;
Indirizzi:
Univ Lausanne, Unit Biochem & Clin Psychopharmacol, Dept Adult Psychiat, Cery Hosp, CH-1008 Prilly Lausanne, Switzerland Univ Lausanne Prilly Lausanne Switzerland CH-1008 Lausanne, Switzerland HUG Belle Idee, Dept Psychiat, Geneva, Switzerland HUG Belle Idee GenevaSwitzerland e, Dept Psychiat, Geneva, Switzerland Psychiat Hosp Prangins, Prangins, Switzerland Psychiat Hosp Prangins Prangins Switzerland gins, Prangins, Switzerland
Titolo Testata:
THERAPEUTIC DRUG MONITORING
fascicolo: 3, volume: 23, anno: 2001,
pagine: 228 - 231
SICI:
0163-4356(200106)23:3<228:PDIPOR>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLASMA-CONCENTRATIONS; CLOZAPINE; METABOLISM; CYP1A2; 9-HYDROXYRISPERIDONE; THIORIDAZINE; DISPOSITION; ENZYMES; CYP3A4; 2D6;
Keywords:
risperidone; CYP2DG; CYP1A2; CYP2C19;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Eap, CB Univ Lausanne, Unit Biochem & Clin Psychopharmacol, Dept Adult Psychiat, Cery Hosp, CH-1008 Prilly Lausanne, Switzerland Univ Lausanne Prilly Lausanne Switzerland CH-1008 e, Switzerland
Citazione:
C.B. Eap et al., "Pharmacokinetic drug interaction potential of risperidone with cytochrome P450 isozymes as assessed by the dextromethorphan, the caffeine, and the mephenytoin test", THER DRUG M, 23(3), 2001, pp. 228-231

Abstract

Two published case reports showed that addition of risperidone (I and 2 mg/d) to a clozapine treatment resulted in a strong increase of clozapine plasma levels. As clozapine is metabolized by cytochrome P450 isozymes, a study was initiated to assess the in vivo interaction potential of risperidone on various cytochrome P450 isozymes. Eight patients were phenotyped with dextromethorphan (CYP2D6), mephenytoin (CYP2C19), and caffeine (CYP1A2) before and after the introduction of risperidone. Before risperidone, all eight patients were phenotyped as being extensive metabolizers of CYP2D6 and CYP2C19. Risperidone at dosages between 2 and 6 mg/d does not appear to significantly inhibit CYP1A2 and CYP2C19 in vivo (median plasma paraxanthine/caffeine ratios before and after risperidone: 0.65, 0.69; p = 0.89; median urinary (S)/(R) mephenytoin ratios before and after risperidone:0.11, 0.12; p = 0.75). Although dextromethorphan metabolic ratio is significantly increasedby risperidone (median urinary dextromethorphan/dextrorphan ratios before and after risperidone: 0.010, 0.018; p = 0.042), risperidone can be considered a weak in vivo CYP2D6 inhibitor, as this increase is modest and none ofthe eight patients was changed from an extensive to a poor metabolizer. The reported increase of clozapine concentrations by risperidone can therefore not be explained by an inhibition of CYP1A2, CYP2D6, CYP2C19 or by any combination of the three.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 10:37:03