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Titolo:
Effects of itraconazole on the steady-state plasma concentrations of haloperidol and its reduced metabolite in schizophrenic patients: In vivo evidence of the involvement of CYP3A4 for haloperidol metabolism
Autore:
Yasui, N; Kondo, T; Otani, K; Furukori, H; Mihara, K; Suzuki, A; Kaneko, S; Inoue, Y;
Indirizzi:
Hirosaki Univ, Sch Med, Dept Neuropsychiat, Hirosaki, Aomori 036, Japan Hirosaki Univ Hirosaki Aomori Japan 036 hiat, Hirosaki, Aomori 036, Japan Yamagata Univ, Sch Med, Dept Neuropsychiat, Yamagata, Japan Yamagata UnivYamagata Japan h Med, Dept Neuropsychiat, Yamagata, Japan Yoshitomi Pharmaceut Ind Ltd, Pharmacol Technol Ctr, Fukuoka, Japan Yoshitomi Pharmaceut Ind Ltd Fukuoka Japan Technol Ctr, Fukuoka, Japan
Titolo Testata:
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
fascicolo: 2, volume: 19, anno: 1999,
pagine: 149 - 154
SICI:
0271-0749(199904)19:2<149:EOIOTS>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEBRISOQUINE HYDROXYLATION PHENOTYPE; SYSTEMIC ANTIMYCOTICS KETOCONAZOLE; AZOLE ANTIFUNGAL AGENTS; MICROSOMES IN-VITRO; HUMAN-LIVER; POOR METABOLIZERS; INHIBITION; TRIAZOLAM; CYP2D6; NEUROTOXICITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Kondo, T Hirosaki Univ, Sch Med, Dept Neuropsychiat, Hirosaki, Aomori 036,Japan Hirosaki Univ Hirosaki Aomori Japan 036 osaki, Aomori 036, Japan
Citazione:
N. Yasui et al., "Effects of itraconazole on the steady-state plasma concentrations of haloperidol and its reduced metabolite in schizophrenic patients: In vivo evidence of the involvement of CYP3A4 for haloperidol metabolism", J CL PSYCH, 19(2), 1999, pp. 149-154

Abstract

The effects of itraconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4, on the steady-state plasma concentrations of haloperidol and reduced haloperidol were examined in schizophrenic patients. Thirteen schizophrenic patients treated with haloperidol 12 or 24 mg/day received 200 mg/day of itraconazole for 7 days. Plasma concentrations of haloperidol and reduced haloperidol were measured by high-performance liquid chromatography together with clinical assessment by the Brief Psychiatric Rating Scale (BPRS) and theUdvalg for Kliniske Undersogelser side effect rating scale just before andduring itraconazole treatment and 1 week after its discontinuation. Plasmaconcentrations of haloperidol and reduced haloperidol during the itraconazole treatment (16.9 +/- 11.2 and 6.1 +/- 6.6 ng/mL, respectively) were significantly (p < 0.01) higher than those observed before itraconazole treatment (13.0 +/- 7.9 and 4.9 +/- 5.1 ng/mL) or 1 week after its discontinuation(13.5 +/- 8.2 and 4.9 +/- 5.0 ng/mL). No change was found in clinical symptoms assessed by BPRS, whereas neurologic side effects were significantly (p < 0.05) increased during itraconazole coadministration. The elevated plasma concentrations of haloperidol and reduced haloperidol during itraconazole coadministration were likely due to the inhibitory effects of itraconazole on the metabolism of haloperidol and reduced haloperidol. Thus, this study may provide in vivo evidence of involvement of CYP3A4 in the metabolism of haloperidol and possibly in that of reduced haloperidol. Deterioration ofneurologic side effects during itraconazole treatment may result from the increased plasma concentrations of haloperidol and reduced haloperidol during itraconazole treatment.

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Documento generato il 23/01/20 alle ore 13:12:36