Impact of the ultrarapid CYP2C19*17 allele on serum concentration of escitalopram in psychiatric patients.
Clin Pharmacol Ther
; 83(2): 322-7, 2008 Feb.
Article
em En
| MEDLINE
| ID: mdl-17625515
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Hidrocarboneto de Aril Hidroxilases
/
Citalopram
/
Inibidores Seletivos de Recaptação de Serotonina
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Antidepressivos de Segunda Geração
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Oxigenases de Função Mista
/
Transtornos Mentais
Tipo de estudo:
Diagnostic_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Noruega