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Impact of the Ultrarapid CYP2C19*17 Allele on Serum Concentration of Escitalopram in Psychiatric Patients
Author(s) -
Rudberg I,
Mohebi B,
Hermann M,
Refsum H,
Molden E
Publication year - 2008
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100291
Subject(s) - cyp2c19 , escitalopram , allele , genotype , medicine , pharmacology , gastroenterology , biology , genetics , gene , antidepressant , hippocampus
Recently, a novel allelic variant of cytochrome P 450 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. Clinical Pharmacology & Therapeutics (2008) doi: 10.1038/sj.clpt.6100291