title: Risperidone and Venlafaxine Metabolic Ratios Strongly Predict a CYP2D6 Poor Metabolizing Genotype.
abstract: OBJECTIVE
  To investigate the predictive value of the risperidone and venlafaxine metabolic ratios and CYP2D6 genotype.
  
  
  METHODS
  The determination of risperidone, 9-hydroxyrisperidone, and venlafaxine, O-desmethylvenlafaxine, N-desmethylvenlafaxine and CYP2D6 genotype was performed in 425 and 491 patients, respectively. The receiver operator characteristic method and the area under the receiver operator characteristic curve were used to illustrate the predictive value of risperidone metabolic ratio for the individual CYP2D6 genotype. To evaluate the proposed cutoff levels of >1 to identify individuals with a poor CYP2D6 genotype, the sensitivity, specificity, positive predictive values, and negative predictive values were calculated.
  
  
  RESULTS
  Area under the receiver operator characteristic curve to predict poor metabolizers for risperidone/9-hydroxyrisperidone and N-desmethylvenlafaxine/O-desmethylvenlafaxine ratios was 93% and 99%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value (confidence interval) of a risperidone/9-hydroxyrisperidone ratio >1 to predict a CYP2D6 poor metabolizer genotype were 91% (76%-97%), 86% (83%-89%), 35% (26%-46%), and 99% (97%-100%), respectively. The corresponding measures for N-desmethylvenlafaxine/O-desmethylvenlafaxine were 93% (76%-97%), 87% (83%-89%), 40% (32%-51%), and 99% (98%-100%).
  
  
  CONCLUSIONS
  Risperidone/9-hydroxyrisperidone and N-desmethylvenlafaxine/O-desmethylvenlafaxine metabolic ratios >1 strongly predict individuals with poor metabolizer genotype, which could guide psychotropic drug treatment to avoid adverse drug reactions and to increase their therapeutic efficacy in patients prescribed these drugs.
authors.affiliation: *Karolinska Institutet, Department of Clinical Science and Education at Södersjukhuset, Stockholm, Sweden; †Department of Pharmacology, Center for Psychopharmacology, Diakonhjemmet Hospital, School of Pharmacy, University of Oslo, Blindern, Norway; ‡Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; and §Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Norway.
authors.forename: Buster
authors.initials: B
authors.lastname: Mannheimer
authors.forename: Tore
authors.initials: T
authors.lastname: Haslemo
authors.forename: Jonatan D
authors.initials: JD
authors.lastname: Lindh
authors.forename: Erik
authors.initials: E
authors.lastname: Eliasson
authors.forename: Espen
authors.initials: E
authors.lastname: Molden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018687:Antidepressive Agents, Second-Generation / Q000493:pharmacokinetics; D014150:Antipsychotic Agents / Q000493:pharmacokinetics; D002648:Child; D003511:Cyclohexanols / Q000493:pharmacokinetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D000069468:Desvenlafaxine Succinate / Q000493:pharmacokinetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate / Q000493:pharmacokinetics; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018967:Risperidone / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D000069470:Venlafaxine Hydrochloride / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D003511:Cyclohexanols; C434332:N-desmethylvenlafaxine; D000069470:Venlafaxine Hydrochloride; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone; D000068882:Paliperidone Palmitate; D000069468:Desvenlafaxine Succinate