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  • Huezo-Diaz, P (author)

CYP2C19 genotype predicts steady state escitalopram concentration in GENDEP

  • Article/chapterEnglish2012

Publisher, publication year, extent ...

  • 2011-09-17
  • SAGE Publications,2012

Numbers

  • LIBRIS-ID:oai:prod.swepub.kib.ki.se:124167333
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:124167333URI
  • https://doi.org/10.1177/0269881111414451DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • In vitro work shows CYP2C19 and CYP2D6 contribute to the metabolism of escitalopram to its primary metabolite, N-desmethylescitalopram. We report the effect of CYP2C19 and CYP2D6 genotypes on steady state morning concentrations of escitalopram and N-desmethylescitalopram and the ratio of this metabolite to the parent drug in 196 adult patients with depression in GENDEP, a clinical pharmacogenomic trial. Subjects who had one CYP2D6 allele associated with intermediate metabolizer phenotype and one associated with poor metabolizer (i.e. IM/PM genotypic category) had a higher mean logarithm escitalopram concentration than CYP2D6 extensive metabolizers (EMs) ( p = 0.004). Older age was also associated with higher concentrations of escitalopram. Covarying for CYP2D6 and age, we found those homozygous for the CYP2C19*17 allele associated with ultrarapid metabolizer (UM) phenotype had a significantly lower mean escitalopram concentration (2-fold, p = 0.0001) and a higher mean metabolic ratio ( p = 0.0003) than EMs, while those homozygous for alleles conferring the PM phenotype had a higher mean escitalopram concentration than EMs (1.55-fold, p = 0.008). There was a significant overall association between CYP2C19 genotypic category and escitalopram concentration ( p = 0.0003; p = 0.0012 Bonferroni corrected). In conclusion, we have demonstrated an association between CYP2C19 genotype, including the CYP2C19*17 allele, and steady state escitalopram concentration.

Added entries (persons, corporate bodies, meetings, titles ...)

  • Perroud, N (author)
  • Spencer, EP (author)
  • Smith, R (author)
  • Sim, SKarolinska Institutet (author)
  • Virding, S (author)
  • Uher, R (author)
  • Gunasinghe, C (author)
  • Gray, J (author)
  • Campbell, D (author)
  • Hauser, J (author)
  • Maier, W (author)
  • Marusic, A (author)
  • Rietschel, M (author)
  • Perez, J (author)
  • Giovannini, C (author)
  • Mors, O (author)
  • Mendlewicz, J (author)
  • McGuffin, P (author)
  • Farmer, AE (author)
  • Ingelman-Sundberg, MKarolinska Institutet (author)
  • Craig, IW (author)
  • Aitchison, KJ (author)
  • Karolinska Institutet (creator_code:org_t)

Related titles

  • In:Journal of psychopharmacology (Oxford, England): SAGE Publications26:3, s. 398-4071461-72850269-8811

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