title: Effects of the CYP2D6*10 allele on the steady-state plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, in Japanese patients with schizophrenia.
abstract: The CYP2D6*10(*10) allele that causes decreased CYP2D6 activity is present in Asians with a high frequency of approximately 50%. We studied the effects of the *10 allele on the steady-state plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole. The subjects were 63 Japanese patients with schizophrenia who had only the wild-type or *10 alleles. Twenty-seven patients were homozygous for the wild-type allele, 31 were heterozygous, and five were homozygous for the *10 allele. All patients had been receiving the fixed doses of aripiprazole for at least 2 weeks. The daily doses were 24 mg (n = 40) and 12 mg (n = 23). No other drugs except biperiden and flunitrazepam were coadministered. Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass spectrometric detection. The mean ± standard deviation values of concentration/dose ratios of aripiprazole in the patients with zero, one, and two *10 alleles were 9.0 ± 2.9, 12.7 ± 4.4, and 19.0 ± 6.8 ng/mL/mg, respectively, and those values for dehydroaripiprazole were 4.9 ± 1.6, 5.9 ± 1.7, and 5.9 ± 1.9 ng/mL/mg, respectively. The respective values for the sum of aripiprazole and dehydroaripiprazole were 13.9 ± 4.3, 18.6 ± 5.9, and 24.6 ± 8.5 ng/mL/mg. The mean concentration/dose ratios of aripiprazole were significantly (P < 0.01 or P < 0.001) different among the three genotype groups. The values for the sum of aripiprazole and dehydroaripiprazole were significantly higher in patients with one (P < 0.01) and two (P < 0.001) *10 alleles compared with those with zero *10 alleles. This study suggests that the *10 allele plays an important role in controlling the steady-state plasma concentrations of aripiprazole and the sum of aripiprazole and dehydroaripiprazole in Asian subjects.
authors.affiliation: Department of Neuropsychiatry, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Mihara
authors.forename: Akifumi
authors.initials: A
authors.lastname: Nakamura
authors.forename: Goyo
authors.initials: G
authors.lastname: Nagai
authors.forename: Shoko
authors.initials: S
authors.lastname: Kagawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Nemoto
authors.forename: Ikuya
authors.initials: I
authors.lastname: Ohta
authors.forename: Hajime
authors.initials: H
authors.lastname: Arakaki
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Uno
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kondo
mesh_terms: D000483:Alleles; D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use; D000068180:Aripiprazole; D044466:Asian People / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D016903:Drug Monitoring; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010879:Piperazines / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use; D015363:Quinolones / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; C517414:dehydroaripiprazole; D000068180:Aripiprazole; D019389:Cytochrome P-450 CYP2D6