title: Influence of CYP2D6 genotype and medication on the sparteine metabolic ratio of psychiatric patients.
abstract: OBJECTIVE
  To investigate the influence of CYP2D6 genotype and medication on the reliability of phenotyping in a naturalistic setting of psychiatric inpatients.
  
  
  METHODS
  The phenotype of 160 psychiatric inpatients was estimated by taking the urinary metabolic ratio (MR) of the concentrations of sparteine to 2- and 5-dehydrosparteine. Genotyping identified CYP2D6*1, *3, *4, *5 and *6 alleles as well as duplication of the CYP2D6 gene. All subjects underwent detailed drug history including drug dose and therapeutic drug monitoring to control compliance and abuse of other psychotropic drugs. These data were compared with those of 195 unmedicated healthy Germans.
  
  
  RESULTS
  The cumulative distribution of the MR in patients showed a significant shift to higher MR when compared with that of healthy subjects (P < or = 0.001). Patients medicated either with selective serotonin reuptake inhibitors (SSRIs, P < or = 0.001), antipsychotic drugs (P= 0.002) or other drugs known to be substrates or inhibitors of CYP2D6 (P < or = 0.001) showed a significantly higher mean MR than unmedicated patients. However, there was no significant effect of tricyclic antidepressants on the MR. Healthy subjects with CYP2D6 deficiency were separated by a MR of greater than 20 from those who expressed functional CYP2D6. Seven patients carrying at least one functional CYP2D6 allele revealed a MR of greater than 20, indicating the occurrence of phenocopying.
  
  
  CONCLUSIONS
  The results of phenotyping may be falsified by drugs known to be substrates or inhibitors of CYP2D6; thus, this method is not sufficiently reliable. However, since we observed the phenomenon of phenocopying only in patients treated with a SSRI such as fluoxetine, fluvoxamine or paroxetine, we conclude that sparteine phenotyping of medicated patients detects CYP2D6 deficiency correctly, provided that patients treated with these SSRIs are excluded.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Germany.
authors.forename: P L
authors.initials: PL
authors.lastname: Lohmann
authors.forename: M L
authors.initials: ML
authors.lastname: Rao
authors.forename: M
authors.initials: M
authors.lastname: Ludwig
authors.forename: E U
authors.initials: EU
authors.lastname: Griese
authors.forename: U M
authors.initials: UM
authors.lastname: Zanger
authors.forename: K
authors.initials: K
authors.lastname: Mörike
authors.forename: W
authors.initials: W
authors.lastname: Maier
authors.forename: M
authors.initials: M
authors.lastname: Bagli
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000494:pharmacology*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013034:Sparteine / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine
chemical_list: D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6; D017367:Selective Serotonin Reuptake Inhibitors; D013034:Sparteine