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Titolo:
The effect of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramine in Japanese psychiatric patients
Autore:
Yokono, A; Morita, S; Someya, T; Hirokane, G; Okawa, M; Shimoda, K;
Indirizzi:
Shiga Univ Med Sci, Dept Psychiat, Otsu, Shiga 5202192, Japan Shiga Univ Med Sci Otsu Shiga Japan 5202192 t, Otsu, Shiga 5202192, Japan Nagahama Seijukai Hosp, Shiga, Japan Nagahama Seijukai Hosp Shiga JapanNagahama Seijukai Hosp, Shiga, Japan Niigata Univ, Grad Sch Med & Dent Sci, Dept Psychiat, Niigata, Japan Niigata Univ Niigata Japan ed & Dent Sci, Dept Psychiat, Niigata, Japan Takashima Gen Hosp, Psychiat Serv, Shiga, Japan Takashima Gen Hosp ShigaJapan ma Gen Hosp, Psychiat Serv, Shiga, Japan
Titolo Testata:
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
fascicolo: 6, volume: 21, anno: 2001,
pagine: 549 - 555
SICI:
0271-0749(200112)21:6<549:TEOCAC>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
STATE PLASMA-CONCENTRATIONS; RAT-LIVER MICROSOMES; DEBRISOQUINE HYDROXYLATION; GENETIC-ANALYSIS; S-MEPHENYTOIN; PRONOUNCED DIFFERENCES; DEPRESSED-PATIENTS; N-DEMETHYLATION; NATIVE CHINESE; POLYMORPHISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Shimoda, K Shiga Univ Med Sci, Dept Psychiat, Otsu, Shiga 5202192, Japan Shiga Univ Med Sci Otsu Shiga Japan 5202192 iga 5202192, Japan
Citazione:
A. Yokono et al., "The effect of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramine in Japanese psychiatric patients", J CL PSYCH, 21(6), 2001, pp. 549-555

Abstract

In this study, the authors investigated the relationship between the metabolism of clomipramine (C) and the genotypes of cytochrome P450 (CYP) CYP2C19 and CYP2D6. Fifty-one Japanese patients (18 men and 33 women) were administered 10 to 250 mg/day of C by mouth and maintained on the same daily doseof C for at least 2 weeks to obtain steady-state concentrations. Plasma levels of C and its metabolites N-desmethylclomipramine (DC), 8-hydroxyclomipramine, and 8-hydroxy-N-desmethylclomipramine (HDC) were determined by high-performance liquid chromatography. The allele frequencies of CYP2C19*2, CYP2C19*3, CYP2D6*5, and CYP2D6*10 were 27.5%, 12.8%, 2.9%, and 43.1%, respectively. Subjects who were homozygous for mutated alleles of CYP2C19 showed approximately 75% higher concentrations of C corrected by dose and body weight compared with those who were homozygous for wild-type alleles. Also, subjects who were homozygous for mutated alleles of CYP2C19 showed an approximately 68% higher value of C/DC compared with those who were homozygous forwild-type alleles. No significant difference in the ratio of DC/HDC was observed between subjects who were homozygous for mutated alleles of CYP2D6 and those who were homozygous for wild-type alleles. These results suggest that genotyping CYP2C19 is useful for grossly predicting the risk of gettinghigh plasma concentrations of C and the low individual capacity to demethylate C because there is marked interindividual variability within each genotype. However, the genotyping of CYP2D6 is not useful for predicting the individual capacity to hydroxylate DC.

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Documento generato il 26/01/20 alle ore 10:56:28