title: Lack of correlation between the steady-state plasma concentrations of aripiprazole and haloperidol in Japanese patients with schizophrenia.
abstract: BACKGROUND
  Both aripiprazole and haloperidol have been used in the treatment of schizophrenia, and are metabolized by the cytochrome P450 (CYP) 2D6 and CYP3A4. The authors studied the correlations between the steady-state plasma concentrations (Css) of aripiprazole and its active metabolite, dehydroaripiprazole, and those of haloperidol in 19 Japanese patients with schizophrenia, together with the effects of CYP2D6 genotypes on the steady-state kinetics of these compounds.
  
  
  METHODS
  All the patients received first 24 mg/d of aripiprazole for 3 weeks and later received 6 mg/d of haloperidol for 2 weeks. Blood samplings were performed at least 2 weeks after the initiation of each treatment. The Css values of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass spectrometric detection, and those of haloperidol were measured by using an enzyme immunoassay. CYP2D6 genotypes were determined by using polymerase chain reaction analysis.
  
  
  RESULTS
  None of the correlations between the Css of aripiprazole (r = 0.286) or the sum of aripiprazole plus dehydroaripiprazole (r = 0.344) and those of haloperidol were significant. The mean Css of aripiprazole was significantly higher (P < 0.05) in the subjects with 1 *10 allele of CYP2D6 (n = 6) than in those with no mutated alleles (n = 13), whereas there were no significant differences in those of haloperidol between the 2 groups.
  
  
  CONCLUSIONS
  This study suggests that the Css of aripiprazole and that of aripiprazole plus dehydroaripiprazole do not correlate with that of haloperidol in the same individual, because of the greater involvement of CYP2D6 in the metabolism of aripiprazole than in that of haloperidol.
authors.affiliation: Departments of *Neuropsychiatry; and †Pharmacy, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Nakamura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Mihara
authors.forename: Kenji
authors.initials: K
authors.lastname: Nemoto
authors.forename: Goyo
authors.initials: G
authors.lastname: Nagai
authors.forename: Shoko
authors.initials: S
authors.lastname: Kagawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kondo
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use; D000068180:Aripiprazole; D044466:Asian People / Q000235:genetics; D005260:Female; D006220:Haloperidol / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000097:blood* / Q000627:therapeutic use; D015363:Quinolones / Q000097:blood* / Q000627:therapeutic use; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy / Q000235:genetics
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole; D006220:Haloperidol