Impact of the ultrarapid CYP2C19*17 allele on serum concentration of escitalopram in psychiatric patients

Clin Pharmacol Ther. 2008 Feb;83(2):322-7. doi: 10.1038/sj.clpt.6100291. Epub 2007 Jul 11.

Abstract

Recently, a novel allelic variant of cytochrome P450 2C19 encoding ultrarapid enzyme activity was described (denoted CYP2C19*17). The objective of this study was to evaluate the impact of CYP2C19*17 on serum concentration of escitalopram in psychiatric patients. One hundred and sixty-six patients treated with escitalopram were divided into the following subgroups according to CYP2C19 genotype: CYP2C19*17/*17 (n=7), CYP2C19*1/*17 (n=43), CYP2C19*1/*1 (n=60), CYP2C19*17/def (n=16), CYP2C19*1/def (n=34), and CYP2C19def/def (n=6) (def=defective allele, i.e., CYP2C19*2 or *3). Dose-adjusted serum concentrations of escitalopram were compared using the CYP2C19*1/*1 subgroup as reference. Geometric mean of the escitalopram serum concentration was 42% lower in patients homozygous for CYP2C19*17 (P<0.01) and 5.7-fold higher in subjects homozygous for defective CYP2C19 alleles (P<0.001). Of the heterozygous subgroups, only CYP2C19*1/def was significantly different from CYP2C19*1/*1 (P<0.001). In conclusion, a homozygous CYP2C19*17 genotype is associated with lower serum concentration of escitalopram, which might imply increased risk of therapeutic failure.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Antidepressive Agents, Second-Generation / administration & dosage
  • Antidepressive Agents, Second-Generation / blood
  • Antidepressive Agents, Second-Generation / pharmacokinetics*
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Citalopram / administration & dosage
  • Citalopram / blood
  • Citalopram / pharmacokinetics*
  • Cytochrome P-450 CYP2C19
  • Female
  • Gene Frequency
  • Genotype
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Mental Disorders / drug therapy*
  • Mental Disorders / enzymology
  • Mental Disorders / genetics
  • Middle Aged
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism
  • Phenotype
  • Polymorphism, Genetic*
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / blood
  • Selective Serotonin Reuptake Inhibitors / pharmacokinetics*
  • Treatment Failure

Substances

  • Antidepressive Agents, Second-Generation
  • Serotonin Uptake Inhibitors
  • Citalopram
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19