par Huezo-Diaz, Patricia;Perroud, Nader;Spencer, Edgar E.P.;Smith, Robert Peter;Sim, Sarah;Virding, Susanne;Uher, Rudolf;Gunasinghe, Cerisse;Gray, Jonathon;Campbell, Desmond;Hauser, Joanna Wiktoria;Maier, Wolfgang;Marusic, Andrej;Rietschel, Marcella;Perez, Jorge Coarasa;Giovannini, Caterina;Mors, Ole;Mendlewicz, Julien ;McGuffin, Peter;Farmer, Anne;Ingelman-Sundberg, Magnus;Craig, Ian;Aitchison, Katherine
Référence Journal of psychopharmacology, 26, 3, page (398-407)
Publication Publié, 2012-03
Référence Journal of psychopharmacology, 26, 3, page (398-407)
Publication Publié, 2012-03
Article révisé par les pairs
Résumé : | 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. © 2012 British Association for Psychopharmacology. |