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CYP2C19 UM

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https://www.readbyqxmd.com/read/27650615/the-diagnostic-utility-of-the-point-of-care-cyp2c19-genotyping-assay-in-patients-with-acute-coronary-syndrome-dosing-clopidogrel-comparison-with-platelet-function-test-and-snp-genotyping
#1
Jae-Lim Choi, Bo-Ram Kim, Kwang-Sook Woo, Kyeong-Hee Kim, Jeong-Man Kim, Moo-Hyun Kim, Jin-Yeong Han
BACKGROUND: Clopidogrel is a widely used antiplatelet agent for dual antiplatelet therapy and metabolized by CYP2C19. The polymorphism of CYP2C19 is associated with the therapeutic effect of clopidogrel. METHODS: A total of 119 patients diagnosed with acute coronary syndrome (ACS) and underwent percutaneous coronary intervention (PCI) with drug-eluting stents was enrolled. Polymorphisms of CYP2C19 *2,*3,*17 were determined by the Spartan RX CYP2C19 and confirmed by SNP genotyping assay...
September 2016: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/25558073/putting-cyp2c19-genotyping-to-the-test-utility-of-pharmacogenomic-evaluation-in-a-voriconazole-treated-haematology-cohort
#2
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
https://www.readbyqxmd.com/read/25520127/improved-eradication-rate-of-standard-triple-therapy-by-adding-bismuth-and-probiotic-supplement-for-helicobacter-pylori-treatment-in-thailand
#3
RANDOMIZED CONTROLLED TRIAL
Chanagune Srinarong, Sith Siramolpiwat, Arti Wongcha-um, Varocha Mahachai, Ratha-korn Vilaichone
BACKGROUND: Helicobacter pylori (H. pylori) remains an important cause of gastric cancer and peptic ulcer disease worldwide. Treatment of H. pylori infection is one of the effective ways to prevent gastric cancer. However, standard triple therapy for H. pylori eradication is no longer effective in many countries, including Thailand. This study was designed to evaluate the efficacy of adding bismuth and probiotic to standard triple therapy for H. pylori eradication. MATERIALS AND METHODS: In this prospective single center study, H...
2014: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/25200585/clinical-applications-of-cyp-genotyping-in-psychiatry
#4
REVIEW
Edoardo Spina, Jose de Leon
A critical review of the limited available evidence and the authors' experience and judgment are used to summarize the role of cytochrome P450 (CYP) genetic variants in the pharmacokinetics of and clinical response to psychotropic medications. CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 genetic polymorphisms and their contributions to the metabolism of psychotropic drugs are reviewed. CYP1A2, CYP2B6 and CYP3A4 genotyping have limited current clinical utility. CYP2C9 genotyping has no utility in psychiatry...
January 2015: Journal of Neural Transmission
https://www.readbyqxmd.com/read/25154506/impact-of-cytochrome-p450-2c19-polymorphisms-on-citalopram-escitalopram-exposure-a-systematic-review-and-meta-analysis
#5
REVIEW
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
https://www.readbyqxmd.com/read/24739523/prediction-of-inter-individual-variability-in-the-pharmacokinetics-of-cyp2c19-substrates-in-humans
#6
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
https://www.readbyqxmd.com/read/24617511/evaluation-of-the-innovance-pfa-p2y-assay-and-its-association-with-cyp2c19-genotypes
#7
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
https://www.readbyqxmd.com/read/24046523/genotype-phenotype-analysis-of-cyp2c19-in-healthy-saudi-individuals-and-its-potential-clinical-implication-in-drug-therapy
#8
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
https://www.readbyqxmd.com/read/24009042/enhanced-active-metabolite-generation-and-platelet-inhibition-with-prasugrel-compared-to-clopidogrel-regardless-of-genotype-in-thienopyridine-metabolic-pathways
#9
RANDOMIZED CONTROLLED TRIAL
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
https://www.readbyqxmd.com/read/23588782/applications-of-cyp450-testing-in-the-clinical-setting
#10
REVIEW
C F Samer, K Ing Lorenzini, V Rollason, Y Daali, J A Desmeules
Interindividual variability in drug response is a major clinical problem. Polymedication and genetic polymorphisms modulating drug-metabolising enzyme activities (cytochromes P450, CYP) are identified sources of variability in drug responses. We present here the relevant data on the clinical impact of the major CYP polymorphisms (CYP2D6, CYP2C19 and CYP2C9) on drug therapy where genotyping and phenotyping may be considered, and the guidelines developed when available. CYP2D6 is responsible for the oxidative metabolism of up to 25% of commonly prescribed drugs such as antidepressants, antipsychotics, opioids, antiarrythmics and tamoxifen...
June 2013: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/23260377/genetic-determinants-of-clopidogrel-responsiveness-in-koreans-treated-with-drug-eluting-stents
#11
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
https://www.readbyqxmd.com/read/22775532/the-amplichip%C3%A2-cyp450-test-and-response-to-treatment-in-schizophrenia-and-obsessive-compulsive-disorder-a-pilot-study-and-focus-on-cases-with-abnormal-cyp2d6-drug-metabolism
#12
Daniel J Müller, Eva J Brandl, Rudi Hwang, Arun K Tiwari, Jessica E Sturgess, Clement C Zai, Jeffrey A Lieberman, James L Kennedy, Margaret A Richter
AIM: Genetic factors can result in variance in drug metabolism enzyme function, which is one major mechanism impacting on interindividual variability in response and side effects. We therefore performed a pilot study to investigate genetic variants in the drug metabolizing enzymes CYP2D6 and CYP2C19. METHODS: We evaluated 35 schizophrenic and 39 obsessive compulsive disorder (OCD) patients treated with various antipsychotics and antidepressants. Patients were assessed for treatment response and side effects...
August 2012: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/22004687/effects-of-omeprazole-and-genetic-polymorphism-of-cyp2c19-on-the-clopidogrel-active-metabolite
#13
RANDOMIZED CONTROLLED TRIAL
Xavier Boulenc, Nassim Djebli, Juan Shi, Laurent Perrin, William Brian, Robert Van Horn, Fabrice Hurbin
Clopidogrel is an antiplatelet agent widely used in cardiovascular diseases and an inactive prodrug that needs to be converted to an active metabolite in two sequential metabolic steps. Several CYP450 isoforms involved in these two steps have been described, although the relative contribution in vivo of each enzyme is still under debate. CYP2C19 is considered to be the major contributor to active metabolite formation. In the current study, net CYP2C19 contribution to the active metabolite formation was determined from exposure of the active metabolite in two clinical studies (one phase I study with well balanced genetic polymorphic populations and a meta-analysis with a total of 396 healthy volunteers) at different clopidogrel doses...
January 2012: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/21984116/feasibility-of-pharmacy-initiated-pharmacogenetic-screening-for-cyp2d6-and-cyp2c19
#14
J J Swen, T van der Straaten, J A M Wessels, M L Bouvy, E E W Vlassak, W J J Assendelft, H-J Guchelaar
PURPOSE: Our purpose was to investigate the feasibility of pharmacy-initiated pharmacogenetic (PGt) screening in primary care with respect to patient willingness to participate, quality of DNA collection with saliva kits, genotyping, and dispensing data retrieved from the pharmacy. METHODS: Polypharmacy patients aged >60 years who used at least one drug with Anatomical Therapeutic Chemical (ATC) code N06AA01-N06AX19 (antidepressants), A02BC01-A02BC05 (proton-pump inhibitors), N05AA01-N05AH04 (antipsychotics), or C07AB02 (metoprolol) in the preceding 2 years were randomly selected...
April 2012: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/21926427/cyp2c19-genotype-predicts-steady-state-escitalopram-concentration-in-gendep
#15
MULTICENTER STUDY
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
https://www.readbyqxmd.com/read/20309015/efficacy-of-tamoxifen-based-on-cytochrome-p450-2d6-cyp2c19-and-sult1a1-genotype-in-the-italian-tamoxifen-prevention-trial
#16
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
https://www.readbyqxmd.com/read/17908053/pharmacogenetic-aspects-of-therapy-with-cholinesterase-inhibitors-the-role-of-cyp2d6-in-alzheimer-s-disease-pharmacogenetics
#17
REVIEW
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
https://www.readbyqxmd.com/read/15177309/allele-and-genotype-frequencies-of-cyp2c9-cyp2c19-and-cyp2d6-in-an-italian-population
#18
COMPARATIVE STUDY
Maria Gabriella Scordo, Achille P Caputi, Concetta D'Arrigo, Giuseppina Fava, Edoardo Spina
The polymorphic cytochrome P450 isoenzymes (CYPs) 2C9, 2C19 and 2D6 metabolise many important drugs, as well as other xenobiotics. Their polymorphism gives rise to important interindividual and interethnic variability in the metabolism and disposition of several therapeutic agents and may cause differences in the clinical response to these drugs. In this study, we determined the genotype profile of a random Italian population in order to compare the CYP2C9, CYP2C19 and CYP2D6 allele frequencies among Italians with previous findings in other Caucasian populations...
August 2004: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/12127912/effects-of-herbal-components-on-cdna-expressed-cytochrome-p450-enzyme-catalytic-activity
#19
L Zou, M R Harkey, G L Henderson
We evaluated the effects of 25 purified components of commonly used herbal products on the catalytic activity of cDNA-expressed cytochrome P450 isoforms in in vitro experiments. Increasing concentrations of the compounds were incubated with a panel of recombinant human CYP isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) and their effects on the conversion of specific surrogate substrates measured fluorometrically in a 96-well plate format. For each test substance, the IC50 (the concentration required to inhibit metabolism of surrogate substrates by 50%) was estimated and compared with IC50's for the positive control inhibitory drugs furafylline, sulfaphenazole, tranylcypromine, quinidine, and ketoconazole...
August 16, 2002: Life Sciences
https://www.readbyqxmd.com/read/10574228/effects-of-ginseng-components-on-c-dna-expressed-cytochrome-p450-enzyme-catalytic-activity
#20
G L Henderson, M R Harkey, M E Gershwin, R M Hackman, J S Stern, D M Stresser
Because little is known about the interactions between herbal products and standard medications, the effects of seven ginsenosides and two eleutherosides (active components of the ginseng root) on the catalytic activity of c-DNA expressed cytochrome P450 isoforms were studied in in vitro experiments. Increasing concentrations of ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1 and eleutherosides B and E were incubated with a panel of recombinant human CYP isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) and their effects on the conversion of specific surrogate substrates measured fluorometrically in a 96-well plate format...
1999: Life Sciences
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