Impact of the ultrarapid CYP2C19*17 allele on serum concentration of escitalopram in psychiatric patients.
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.
Rudberg
I
I
Department of Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway. ida.rudberg@diakonsyk.no
Mohebi
B
B
Hermann
M
M
Refsum
H
H
Molden
E
E
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D015283:Citalopram / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011110:Polymorphism, Genetic; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D017211:Treatment Failure
D018687:Antidepressive Agents, Second-Generation; D001189:Aryl Hydrocarbon Hydroxylases; D015283:Citalopram; D065731:Cytochrome P-450 CYP2C19; D006899:Mixed Function Oxygenases; D017367:Selective Serotonin Reuptake Inhibitors; C045793:CYP2C19 protein, human