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Impact of CYP2D6 on serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol.
Waade, Ragnhild Birkeland; Solhaug, Vigdis; Høiseth, Gudrun.
Afiliación
  • Waade RB; Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
  • Solhaug V; Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
  • Høiseth G; Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
Br J Clin Pharmacol ; 87(5): 2228-2235, 2021 05.
Article en En | MEDLINE | ID: mdl-33118660
AIMS: To investigate the impact of cytochrome P450 2D6 (CYP2D6) on dose-adjusted serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol in a therapeutic drug monitoring (TDM) cohort of psychiatric patients. We also studied the functional impact of CYP2D6*41 on dose-adjusted serum concentrations in the perphenazine-treated patients. METHODS: Serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol from CYP-genotyped patients were extracted retrospectively from a routine TDM database in the period March 2005 to May 2019. Samples were divided into three CYP2D6 phenotype subgroups according to genotype; normal metabolizers (NMs), intermediate metabolizers (IMs) and poor metabolizers (PMs). The effect of CYP2D6 phenotype on dose-adjusted serum concentrations of the four antipsychotics was evaluated by multivariable mixed model analyses. RESULTS: Mean dose-adjusted serum concentrations of perphenazine (564 samples) were 3.9-fold and 1.6-fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (P < .001 and P < .01). For zuclopenthixol (658 samples), mean dose-adjusted serum concentrations were about 1.5-fold and 1.3-fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (P < .01 and P < .001). CYP2D6 was of minor or no importance to haloperidol (320 samples) and flupentixol (115 samples). In our data material, the genotype CYP2D6 *1/*41 appears to have a similar impact on dose-adjusted serum concentrations of perphenazine as *1/null (null = variant allele encoding no enzyme function). CONCLUSIONS: This study shows that CYP2D6 is important for the metabolism of perphenazine and zuclopenthixol, but not for haloperidol and flupentixol. The CYP2D6*41 allele appears to have a reduced function close to nonfunctional variant alleles.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Clopentixol / Citocromo P-450 CYP2D6 Tipo de estudio: Observational_studies Límite: Humans Idioma: En Revista: Br J Clin Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: Noruega

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Clopentixol / Citocromo P-450 CYP2D6 Tipo de estudio: Observational_studies Límite: Humans Idioma: En Revista: Br J Clin Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: Noruega