title: Relationship between risperidone and 9-hydroxy-risperidone plasma concentrations and CYP2D6 enzyme activity in psychiatric patients.
abstract: The implication of cytochrome P450 CYP2D6 enzyme activity in the metabolism of the antipsychotic drug risperidone has been reported in vitro and in studies of healthy volunteers. Around 7 % of Caucasians have inherited impaired capacity of this enzyme (poor metabolisers). These subjects might be prone to higher plasma concentrations of risperidone. The aim of the study was to determine the relationship between the debrisoquine metabolic ratio (MR), a marker of CYP2D6 enzyme activity, and risperidone plasma levels in psychiatric patients. A population of 40 Spanish and Hungarian schizophrenic patients was studied. The possible inhibition of CYP2D6 enzyme was also evaluated in a subgroup of patients co-medicated with inhibitors of CYP2D6. The risperidone/9-hydroxy-risperidone ratio correlated significantly with debrisoquine MR (p < 0.001). In patients co-medicated with strong inhibitors of CYP2D6, the plasma levels of risperidone (p < 0.05) and debrisoquine MR (p < 0.01) and risperidone/9-hydroxy-risperidone ratio were higher compared to patients with monotherapy. According to the present data, the evaluation of the risperidone/9-hydroxy-risperidone ratio may reflect the actual enzyme activity of CYP2D6. Therefore, the use of this ratio may help to assess potential pharmacokinetic interactions and to improve risperidone treatment.
authors.affiliation: University of Extremadura, Faculty of Medicine, Department of Pharmacology and Psychiatry, Unit of Research and Clinical Psychopharmacology, Mérida Psychiatric Hospital, Badajoz, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Berecz
authors.forename: A
authors.initials: A
authors.lastname: LLerena
authors.forename: A
authors.initials: A
authors.lastname: de la Rubia
authors.forename: J
authors.initials: J
authors.lastname: Gómez
authors.forename: M
authors.initials: M
authors.lastname: Kellermann
authors.forename: P
authors.initials: P
authors.lastname: Dorado
authors.forename: I
authors.initials: I
authors.lastname: Degrell
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D007555:Isoxazoles / Q000097:blood*; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D010641:Phenotype; D011743:Pyrimidines / Q000097:blood*; D018967:Risperidone / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D044465:White People
chemical_list: D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone; D000068882:Paliperidone Palmitate