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Titolo:
Plasma concentrations of haloperidol are related to CYP2D6 genotype at low, but not high doses of haloperidol in Korean schizophrenic patients
Autore:
Roh, HK; Chung, JY; Oh, DY; Park, CS; Svensson, JO; Dahl, ML; Bertilsson, L;
Indirizzi:
Inha Univ Hosp, Dept Internal Med, Div Clin Pharmacol, Jung Gu 400711, Incheon, South Korea Inha Univ Hosp Jung Gu Incheon South Korea 400711 1, Incheon, South Korea Huddinge Univ Hosp, Karolinska Inst, Div Clin Pharmacol, Dept Med Lab Sci & Technol, Stockholm, Sweden Huddinge Univ Hosp Stockholm Sweden ab Sci & Technol, Stockholm, Sweden Inha Univ, Coll Med, Dept Pharmacol, Inchon, South Korea Inha Univ Inchon South Korea l Med, Dept Pharmacol, Inchon, South Korea Seoul Natl Mental Hosp, Seoul, South Korea Seoul Natl Mental Hosp Seoul South Korea ental Hosp, Seoul, South Korea
Titolo Testata:
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
fascicolo: 3, volume: 52, anno: 2001,
pagine: 265 - 271
SICI:
0306-5251(200109)52:3<265:PCOHAR>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEBRISOQUINE HYDROXYLATION PHENOTYPE; REDUCED HALOPERIDOL; PRONOUNCED DIFFERENCES; POOR METABOLIZERS; S-MEPHENYTOIN; POPULATION; SPARTEINE; JAPANESE; DISPOSITION; OXIDATION;
Keywords:
CYP2D6 genotype; haloperidol; reduced haloperidol; schizophrenic patients;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Roh, HK Inha Univ Hosp, Dept Internal Med, Div Clin Pharmacol, 7-206,3 Ga,Jung Gu400711, Incheon, South Korea Inha Univ Hosp 7-206,3 Ga Jung Gu Incheon South Korea 400711 Korea
Citazione:
H.K. Roh et al., "Plasma concentrations of haloperidol are related to CYP2D6 genotype at low, but not high doses of haloperidol in Korean schizophrenic patients", BR J CL PH, 52(3), 2001, pp. 265-271

Abstract

Aims This study was carried out to evaluate the influence of CYP2D6 genotype on the steady state plasma concentrations of haloperidol and reduced haloperidol in Korean schizophrenic patients. Methods One hundred and twenty Korean schizophrenic patients treated with various, clinically determined, doses of haloperidol (range 3-60, median 20mg day(-1)) during monotherapy were recruited. CYP2D6 genotypes were determined by analysis of the CYP2D6*10 allele using allele-specific PCR and theCYP2D6*5 allele by long-PCR. Steady state plasma concentrations of haloperidol and reduced haloperidol were analysed by h.p.l.c. Results Twenty-three (19.2%), 60 (50.0%), 1 (0.8%), 33 (27.5%) and 3 patients (2.5%) possessed the CYP2D6 genotypes *1/*1, *1/*10, *1/*5, *10/*10 and*10/*5, respectively. The allele frequencies of CYP2D6*1, *10 and *5 were 44.6%, 53.8% and 1.7%, respectively. Significant relationships between doseand plasma concentrations of haloperidol (linear; r(2)=0.60, P<0.0001) andreduced haloperidol (quadratic equation; r(2)=0.67) were observed. Overall, the concentrations normalized for dose (C/D) of haloperidol were significantly different between the CYP2D6*1/*1, *1/*10 and *10/*10 genotype groups(one-way ANOVA; P=0.028). No significant differences between the genotype groups were found with respect to the C/D of reduced haloperidol (P=0.755). However, in patients with daily doses less than 20 mg, significant differences in the C/D of haloperidol (P=0.003), but not of reduced haloperidol, were found between the three major genotype groups. In patients with doses higher than 20 mg, no differences were found between the genotype groups foreither haloperidol or reduced haloperidol. 68 patients (57%) used benztropine, an antimuscarinic agent. All four patients with a *5 allele (one together with *1 and three with *10) were found to use benztropine. The patientshomozygous for the *1 allele seemed to need less benztropine than the patients with one or two mutated alleles (Fisher's exact test; P=0.036). Conclusions The dose-corrected steady state plasma concentrations of haloperidol, but not of reduced haloperidol, were significantly different between the CYP2D6*1/*1, *1/*10 and *10/*10 genotype groups when doses lower than20 mg haloperidol were given. No differences were found at higher doses. These results suggest the involvement of CYP2D6 in the metabolism of haloperidol at low doses of haloperidol (< 20 mg daily), while another enzyme, probably CYP3A4, contributes at higher doses.

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Documento generato il 08/12/19 alle ore 11:51:25