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CYP2C19 UM 1*/*17

J A Trubiano, A Crowe, L J Worth, K A Thursky, M A Slavin
OBJECTIVES: The clinical utility of pharmacogenomic testing in haematology patients with invasive fungal disease (IFD) receiving azole therapy has not been defined. We report our experience with CYP2C19 testing in haematological patients requiring voriconazole therapy for IFD. METHODS: As a single-centre pilot study, 19 consecutive patients with a haematological malignancy undergoing active chemotherapy with a possible, probable or proven IFD requiring voriconazole therapy underwent CYP2C19 testing from 2013 to 2014...
April 2015: Journal of Antimicrobial Chemotherapy
Ming Chang, Gunnel Tybring, Marja-Liisa Dahl, Jonatan D Lindh
BACKGROUND: Citalopram and escitalopram, selective serotonin reuptake inhibitors, are primarily metabolized by cytochrome P450 (CYP) 2C19, which is a highly polymorphic enzyme known to cause inter-individual differences in pharmacokinetics. However, the impact of CYP2C19 polymorphisms on citalopram or escitalopram exposure has yet to be fully clarified, especially with regard to the quantitative impact of the CYP2C19*17 allele. OBJECTIVE: The objective of this study was to quantify the effect of functional CYP2C19 allele variants on citalopram/escitalopram exposure...
September 2014: Clinical Pharmacokinetics
Koji Chiba, Keiko Shimizu, Motohiro Kato, Takaaki Nishibayashi, Kazuki Terada, Nobuo Izumo, Yuichi Sugiyama
Significant inter-individual variability of exposure for CYP2C19 substrates may be only partly due to genetic polymorphism. Therefore, the in vivo inter-individual variability in hepatic intrinsic clearance (CL(int,h)) of CYP2C19 substrates was estimated from reported AUC values using Monte Carlo simulations. The coefficient of variation (CV) for CL(int,h) in poor metabolizers (PM) expected from genotypes CYP2C19*2/*2, CYP2C19*3/*3 or CYP2C19*2/*3 was estimated as 25.8% from the CV for AUC of omeprazole in PMs...
2014: Drug Metabolism and Pharmacokinetics
Hyunjung Kim, Yonggoo Kim, Yoon-Seok Koh, Hae Kyung Lee, Hyojin Chae, Dong Wook Jekarl, Jong-Min Lee, Woo-Seung Shin, Tae-Hoon Kim
The purpose of this study was to evaluate associations between INNOVANCE PFA P2Y (PFA P2Y) test results and CYP2C19 genotypes and provide baseline data for PFA P2Y testing to establish a therapeutic monitoring strategy for clopidogrel. A total of 75 new patients with acute coronary syndrome with planned percutaneous coronary intervention were enrolled between June 2012 and September 2012. All patients received clopidogrel at an initial loading dose of 600 mg followed by a 75-mg daily maintenance dose. Blood samples were obtained on the third morning after clopidogrel loading...
2015: Platelets
Leena H Saeed, Ahmed Y Mayet
UNLABELLED: CYP2C19 is a cytochrome P450 enzyme, which is involved in the metabolism of some clinically important medications and is encoded by a highly polymorphic gene. There is no available data on the distribution of the CYP2C19 *4 and *17 mutant alleles in the Saudi Arabian population. The aim of the study was to determine different CYP2C19 mutant allele (*2, *4 and *17) frequencies in healthy Saudi subjects and to determine genotype frequencies for these mutations. The CYP2C19 genotypes were then classified into phenotypes...
2013: International Journal of Medical Sciences
Oscar Ö Braun, Dominick J Angiolillo, Jose L Ferreiro, Joseph A Jakubowski, Kenneth J Winters, Mark B Effron, Suman Duvvuru, Timothy M Costigan, Scott Sundseth, Joseph R Walker, Jorge F Saucedo, Neal S Kleiman, Christoph Varenhorst
Clopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers)...
December 2013: Thrombosis and Haemostasis
Jin Joo Park, Kyung Woo Park, Jeehoon Kang, Ki-Hyun Jeon, Si-Hyuck Kang, Hyo Suk Ahn, Jung-Kyu Han, Jin-Sin Koh, Sang Eun Lee, Han-Mo Yang, Hae-Young Lee, Hyun-Jae Kang, Bon-Kwon Koo, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
BACKGROUND: Variations of genes encoding cytochrome enzymes, drug transporters, and paraoxonase have recently been reported to be associated with clopidogrel response variability besides the well-known CYP2C19 loss-of-function (LOF) alleles. We determined whether newly reported genetic variations are associated with clopidogrel on-treatment platelet reactivity (OPR) in Korean patients. METHODS: OPR was measured in 1264 consecutive patients who underwent percutaneous coronary intervention using the VerifyNowP2Y12 assay system and genotyping of PON-1 Q192R, ABCB1 C3435T, CYP1A2*1F, CYP2B6*6, CYP2C19*2, CYP2C19*3, CYP2C19*17, CYP3A4 (IVS10+12G>A), and CYP3A5*3 was performed...
February 10, 2013: International Journal of Cardiology
Patricia Huezo-Diaz, Nader Perroud, Edgar P Spencer, Rebecca Smith, Sarah Sim, Susanne Virding, Rudolf Uher, Cerisse Gunasinghe, Jo Gray, Desmond Campbell, Joanna Hauser, Wolfgang Maier, Andrej Marusic, Marcella Rietschel, Jorge Perez, Caterina Giovannini, Ole Mors, Julien Mendlewicz, Peter McGuffin, Anne E Farmer, Magnus Ingelman-Sundberg, Ian W Craig, Katherine J Aitchison
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...
March 2012: Journal of Psychopharmacology
D Serrano, M Lazzeroni, C-F Zambon, D Macis, P Maisonneuve, H Johansson, A Guerrieri-Gonzaga, M Plebani, D Basso, J Gjerde, G Mellgren, N Rotmensz, A Decensi, B Bonanni
The role of pharmacogenomics and tamoxifen was investigated by analyzing several polymorphisms of cytochrome P450 and SULT1A1 gene in a nested case control study from the Italian Tamoxifen Prevention Trial. This study included 182 Caucasian subjects, 47 breast cancer (BC) cases and 135 matched controls. We used the AmpliChip CYP450 Test to screen 33 alleles of CYP2D6 and 3 of CYP2C19. One more variant for CYP2C19*17 and two single-nucleotide polymorphisms for the gene SULT1A1 were also performed. By using the AmpliChip CYP450 Test, out of 182 subjects, we identified 8 poor metabolizer (PM), 17 intermediate metabolizer (IM), 151 extensive metabolizer (EM) and 3 ultrarapid metabolizer (UM)...
April 2011: Pharmacogenomics Journal
Ramón Cacabelos, Ruth Llovo, Carmen Fraile, Lucía Fernández-Novoa
Recent studies demonstrate that the therapeutic response in Alzheimer's disease (AD) is genotype-specific. More than 200 genes are potentially associated with AD pathogenesis and neurodegeneration, and approximately 1,400 genes distributed across the human genome account for 20 to 95% of variability in drug disposition and pharmacodynamics. Cytochrome P450 enzymes encoded by genes of the CYP superfamily, such as CYP1A1 (15q22-q24), CYP2A6 (19q13.2), CYP2C8 (10q24), CYP2C9 (10q24), CYP2C19 (10q24.1-q24.3), CYP2D6 (22q13...
September 2007: Current Alzheimer Research
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