title: Kinetics of omeprazole and escitalopram in relation to the CYP2C19*17 allele in healthy subjects.
abstract: OBJECTIVE
  Ultrarapid drug metabolism of antidepressants has been associated with therapeutic failures. The CYP2C19*17 allele has been associated with higher levels of CYP2C19 gene transcription and increased rates of omeprazole and mephenytoin metabolism. The aim of this study was to compare the impact of the CYP2C19*17 allele on omeprazole single-dose kinetics with escitalopram exposure at steady state in volunteers genotyped as either CYP2C19*17/*17 or CYP2C19*1/*1.
  
  
  METHODS
  Sixteen healthy volunteers participated in both study parts, five homozygous for CYP2C19*17 and 11 homozygous for CYP2C19*1. Individual pharmacokinetic parameters were determined after single-dose omeprazole of 40 mg and after 1 week on escitalopram 5 mg b.i.d.
  
  
  RESULTS
  Escitalopram area under the concentration time curve from zero to 12 h (AUC(0-12h)) was 21% lower in homozygous carriers of CYP2C19*17 compared with CYP2C19*1 (p = 0.08). There was a significant correlation between escitalopram exposure at steady state and the single-dose kinetics of omeprazole (Spearman correlation coefficient of 0.67; p = 0.006).
  
  
  CONCLUSIONS
  Based on our investigation using two different CYP2C19 substrates, we concluded that a clinically significant difference in escitalopram or omeprazole kinetics between the genotypes appears unlikely.
authors.affiliation: Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska University Hospital Huddinge, SE-141 86, Stockholm, Sweden. staffan.ohlsson@ki.se
authors.forename: Staffan
authors.initials: S
authors.lastname: Ohlsson Rosenborg
authors.forename: Jessica
authors.initials: J
authors.lastname: Mwinyi
authors.forename: Maria
authors.initials: M
authors.lastname: Andersson
authors.forename: R Michael
authors.initials: RM
authors.lastname: Baldwin
authors.forename: Rasmus Steen
authors.initials: RS
authors.lastname: Pedersen
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Sim
authors.forename: Leif
authors.initials: L
authors.lastname: Bertilsson
authors.forename: Magnus
authors.initials: M
authors.lastname: Ingelman-Sundberg
authors.forename: Erik
authors.initials: E
authors.lastname: Eliasson
mesh_terms: D000328:Adult; D000483:Alleles; D000897:Anti-Ulcer Agents / Q000097:blood / Q000493:pharmacokinetics*; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D015283:Citalopram / Q000097:blood / Q000493:pharmacokinetics*; D065731:Cytochrome P-450 CYP2C19; D004334:Drug Administration Schedule; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000235:genetics; D008875:Middle Aged; D009853:Omeprazole / Q000097:blood / Q000493:pharmacokinetics*; D013379:Substrate Specificity; D055815:Young Adult
chemical_list: D000897:Anti-Ulcer Agents; D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole