Impact of the Ultrarapid CYP2C19*17 Allele on Serum Concentration of Escitalopram in Psychiatric Patients. Export

@article{citeulike:1601874, 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.Clinical Pharmacology \&\#38; Therapeutics advance online publication 11 July 2007. doi:10.1038/sj.clpt.6100291.}, address = {1Department of Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.}, author = {Rudberg, I and Mohebi, B and Hermann, M and Refsum, H and Molden, E}, citeulike-article-id = {1601874}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/sj.clpt.6100291}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17625515}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17625515}, day = {11}, doi = {10.1038/sj.clpt.6100291}, issn = {0009-9236}, journal = {Clin Pharmacol Ther}, keywords = {anti\_depressant, clinical\_trial, pharmacokinetic}, month = {July}, posted-at = {2007-08-28 21:43:18}, priority = {0}, title = {Impact of the Ultrarapid CYP2C19*17 Allele on Serum Concentration of Escitalopram in Psychiatric Patients.}, url = {http://dx.doi.org/10.1038/sj.clpt.6100291}, year = {2007} }

TY - JOUR ID - citeulike:1601874 L3 - citeulike-article-id:1601874 N2 - 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.Clinical Pharmacology &#38; Therapeutics advance online publication 11 July 2007. doi:10.1038/sj.clpt.6100291. JF - Clin Pharmacol Ther SN - 0009-9236 AD - 1Department of Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway. TI - Impact of the Ultrarapid CYP2C19*17 Allele on Serum Concentration of Escitalopram in Psychiatric Patients. KW - anti_depressant KW - clinical_trial KW - pharmacokinetic AU - Rudberg, I AU - Mohebi, B AU - Hermann, M AU - Refsum, H AU - Molden, E PY - 2007/07/11/ UR - http://dx.doi.org/10.1038/sj.clpt.6100291 ER -