title: Serum concentrations of sertraline and N-desmethyl sertraline in relation to CYP2C19 genotype in psychiatric patients.
abstract: OBJECTIVE
  To investigate the impact of CYP2C19 genotype on serum concentrations of sertraline and N-desmethyl sertraline in psychiatric patients.
  
  
  METHODS
  Patients treated with sertraline (n = 121) were divided into six subgroups according to CYP2C19 genotype: CYP2C19*17/*17, CYP2C19*1/*17, CYP2C19*1/*1, CYP2C19*17/def, CYP2C19*1/def and CYP2C19def/def (def = allele encoding defective CYP2C19 metabolism, i.e. *2 and *3). Dose-adjusted serum concentrations were compared by linear mixed model analyses using the CYP2C19*1/*1 subgroup as reference.
  
  
  RESULTS
  Subgroups carrying one or two alleles encoding defective CYP2C19 metabolism achieved significantly higher mean dose-adjusted serum concentrations of sertraline and N-desmethyl sertraline compared to the CYP2C19*1/*1 subgroup (P < 0.05). The effect of CYP2C19 genotype was expressed as 3.2-fold (sertraline) and 4.5-fold (N-desmethyl sertraline) higher dose-adjusted serum concentrations in the CYP2C19def/def subgroup compared to the CYP2C19*1/*1 subgroup (P < 0.01). The CYP2C19*17 allele had no influence on the dose-adjusted serum concentrations of sertraline and N-desmethyl sertraline.
  
  
  CONCLUSIONS
  The significantly higher serum concentrations associated with alleles encoding defective CYP2C19 metabolism might be of relevance for the clinical outcome of sertraline treatment.
authors.affiliation: Department of Psychopharmacology, Diakonhjemmet Hospital, P.O. Box 85 Vinderen, N-0319, Oslo, Norway. ida.rudberg@diakonsyk.no
authors.forename: I
authors.initials: I
authors.lastname: Rudberg
authors.forename: M
authors.initials: M
authors.lastname: Hermann
authors.forename: H
authors.initials: H
authors.lastname: Refsum
authors.forename: E
authors.initials: E
authors.lastname: Molden
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D008657:Metabolic Clearance Rate / Q000235:genetics; D008875:Middle Aged; D020280:Sertraline / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D053719:Tandem Mass Spectrometry
chemical_list: D000928:Antidepressive Agents; C065162:desmethylsertraline; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D020280:Sertraline