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https://www.readbyqxmd.com/read/28095090/associations-between-rs4244285-and-rs762551-gene-polymorphisms-and-age-related-macular-degeneration
#1
Neringa Stasiukonyte, Rasa Liutkeviciene, Alvita Vilkeviciute, Mantas Banevicius, Loresa Kriauciuniene
BACKGROUND: Age-related macular degeneration is the leading cause of blindness in elderly individuals in developed countries. The etiology and pathophysiology of age-related macular degeneration have not been elucidated yet. Knowing that the main pathological change of age-related macular degeneration is formation of drusen containing about 40% of lipids, there have been attempts to find associations between age-related macular degeneration and genes controlling lipid metabolism. PURPOSE: To determine the frequency of CYP2C19 (G681A) Rs4244285 and CYP1A2 (-163C>A) Rs762551 genotypes in patients with age-related macular degeneration...
January 17, 2017: Ophthalmic Genetics
https://www.readbyqxmd.com/read/28081475/add-on-stiripentol-elevates-serum-valproate-levels-in-patients-with-or-without-concomitant-topiramate-therapy
#2
Toshihiro Jogamoto, Yoshiaki Yamamoto, Mitsumasa Fukuda, Yuka Suzuki, Katsumi Imai, Yukitoshi Takahashi, Yushi Inoue, Yoko Ohtsuka
OBJECTIVE: Stiripentol (STP), valproate (VPA) and topiramate (TPM) are reported to have efficacy for Dravet syndrome. In this study, we sought to elucidate the mechanisms underlying the increased serum VPA concentrations following STP adjunctive therapy in patients with Dravet syndrome. METHODS: Twenty-eight patients with Dravet syndrome (age range, 1-35 years) undergoing combination therapy with VPA and STP were included in this study. We evaluated VPA and clobazam (CLB) serum concentrations before and after add-on STP...
December 26, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/28076455/decreased-platelet-responsiveness-to-clopidogrel-correlates-with-cyp2c19-and-pon1-polymorphisms-in-atherosclerotic-patients
#3
J F M Marchini, M R Pinto, G C Novaes, A V Badran, R B Pavão, G L Figueiredo, I M Lago, M O Lima-Filho, D C Lemos, M Tonani, C M Antloga, L Oliveira, J C Lorenzi, J A Marin-Neto
Clopidogrel and aspirin are the most commonly used medications worldwide for dual antiplatelet therapy after percutaneous coronary intervention. However, clopidogrel hyporesponsiveness related to gene polymorphisms is a concern. Populations with higher degrees of genetic admixture may have increased prevalence of clopidogrel hyporesponsiveness. To assess this, we genotyped CYP2C19, ABCB1, and PON1 in 187 patients who underwent percutaneous coronary intervention. Race was self-defined by patients. We also performed light transmission aggregometry with adenosine diphosphate (ADP) and arachidonic acid during dual antiplatelet therapy...
January 9, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28070995/haplotype-of-platelet-receptor-p2ry12-gene-is-associated-with-residual-clopidogrel-on-treatment-platelet-reactivity
#4
Xiao-Yan Nie, Jun-Lei Li, Yong Zhang, Yang Xu, Xue-Li Yang, Yu Fu, Guang-Kai Liang, Yun Lu, Jian Liu, Lu-Wen Shi
OBJECTIVE: To investigate a possible association between common variations of the P2RY12 and the residual clopidogrel on-treatment platelet reactivity after adjusting for the influence of CYP2C19 tested by thromboelastography (TEG). METHODS: One hundred and eighty patients with acute coronary syndrome (ACS) treated with clopidogrel and aspirin were included and platelet function was assessed by TEG. Five selected P2RY12 single nucleotide polymorphisms (SNPs; rs6798347, rs6787801, rs6801273, rs6785930, and rs2046934), which cover the common variations in the P2RY12 gene and its regulatory regions, and three CYP2C19 SNPs ((*)2,(*)3,(*)17) were genotyped and possible haplotypes were analyzed...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/28070879/a-review-of-pharmacogenetics-of-antimalarials-and-associated-clinical-implications
#5
REVIEW
Hazem Elewa, Kyle John Wilby
Genetic variability in drug-metabolizing enzymes and drug transporters is known to influence the pharmacokinetics of many drugs. Antimalarial drugs are a class of agents known to utilize metabolic and elimination pathways prone to genetic variation. This paper aims to review the genetic variants affecting antimalarial medications and discuss their clinical implications. Data were identified for the genes coding for the cytochrome P450 (CYP) enzymes: CYP2C8, CYP2C19, CYP2A6, CYP2D6, CYP2B6, and the P-glycoprotein drug transporter...
January 9, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28067999/evaluation-of-pharmacokinetic-interactions-between-lesinurad-a-new-selective-urate-reabsorption-inhibitor-and-cyp-enzyme-substrates-sildenafil-amlodipine-tolbutamide-and-repaglinide
#6
Michael Gillen, Chun Yang, David Wilson, Shakti Valdez, Caroline Lee, Bradley Kerr, Zancong Shen
Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of hyperuricemia associated with gout in combination with xanthine oxidase inhibitors. In vitro assays indicate that lesinurad is an inducer of CYPs in the order CYP3A > CYP2C8 > CYP2C9 > CYP2C19 > CYP2B6 and an inhibitor of CYP2C8 and CYP2C9. To investigate the drug interaction potential of lesinurad, clinical drug interaction studies were conducted. Open-label studies in volunteers investigated the effects of single-/multiple-dose lesinurad on the pharmacokinetics of sildenafil and amlodipine (CYP3A4 induction), tolbutamide (CYP2C9 inhibition/induction), and repaglinide (CYP2C8 inhibition/induction)...
January 9, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28066799/the-study-protocol-for-a-non-randomized-controlled-clinical-trial-using-a-genotype-guided-strategy-in-a-dataset-of-patients-who-undergone-percutaneous-coronary-intervention-with-stent
#7
Cristina Lucía Dávila-Fajardo, Jesús Sánchez-Ramos, Xando Diaz- Villamarín, Luis Javier Martínez-González, Pablo Toledo Frías, Susana Martínez Huertas, Francisco Burillo Gómez, Juan Caballero Borrego, Alicia Bautista Pavés, Mª Carmen Marín Guzmán, José Antonio Ramirez Hernández, Concepción Correa Vilches, Jose Cabeza Barrera
This article contains data related to the research article entitled "Results of genotype-guided antiplatelet therapy in patients undergone percutaneous coronary intervention with stent" (J. Sánchez-Ramos, C.L. Dávila-Fajardo, P. Toledo Frías, X. Díaz Villamarín, L.J. Martínez-González, S. Martínez Huertas, F. Burillo Gómez, J. Caballero Borrego, A. Bautista Pavés, M.C. Marín Guzmán, J.A. Ramirez Hernández, C. Correa Vilches, J. Cabeza Barrera, 2016) (1). This data article reports, for the first time, about the non-randomized clinical trial protocol that check if CYP2C19/ABCB1 genotype-guided strategy in which the choice of antiplatelet therapy is based on the genetic test, reduces the rates of cardiovascular events and bleeding compared to a non-tailored strategy in patients undergone percutaneous coronary intervention (PCI) with stent...
February 2017: Data in Brief
https://www.readbyqxmd.com/read/28064328/pharmacogenetics-of-cyp2c19-genetic-polymorphism-on-clopidogrel-response-in-patients-with-ischemic-stroke-from-saudi-arabia
#8
Adel A Alhazzani, Murali Munisamy, Gauthaman Karunakaran
OBJECTIVE: To elucidate the degree of genetic polymorphisms CYP2C19 (CYP2C19*2, CYP2C19*3) of key drug metabolizing enzymes on the antiplatelet effect of clopidogrel response in patients with acute ischemic stroke from Saudi Arabia. METHODS: A case-control study carried out at Neurology Clinics at Asser Central Hospital, Abha, Kingdom of Saudi Arabia from October 2015 to January 2016 and included 25 stroke patients responding to clopidogrel therapy and 25 stroke patients non responding to clopidogrel monotherapy...
January 2017: Neurosciences: the Official Journal of the Pan Arab Union of Neurological Sciences
https://www.readbyqxmd.com/read/28057172/substrate-specificity-of-human-cytochrome-p450-cyp-2c-subfamily-and-effect-of-azole-antifungal-agents-on-cyp2c8
#9
Toshiro Niwa, Yurie Imagawa
PURPOSE: The metabolic activities of aminopyrine N-demethylation and tolbutamide methylhydroxylation by the human hepatic cytochrome P450 (P450 or CYP) 2C subfamily were compared and the effects of azole antifungal agent on the drug-metabolizing activity of CYP2C8 were investigated. METHODS: Aminopyrine N-demethylation and tolbutamide methylhydroxylation by CYP2C8, CYP2C9, and CYP2C19 were determined by the previous reported methods. The effects of five azole antifungal agents, fluconazole, itraconazole, ketoconazole, miconazole, and voriconazole, on the aminopyrine N-demethylation activity by CYP2C8 were investigated...
October 2016: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28056947/triptolide-induces-hepatotoxicity-via-inhibition-of-cyp450s-in-rat-liver-microsomes
#10
Yan Lu, Tong Xie, Yajie Zhang, Fuqiong Zhou, Jie Ruan, Weina Zhu, Huaxu Zhu, Zhe Feng, Xueping Zhou
BACKGROUND: Triptolide (TP), an active constituent of Tripterygium wilfordii, possesses numerous pharmacological activities. However, its effects on cytochrome P450 enzymes (CYP450s) in rats remain unexplored. METHODS: In this study, the effects of triptolide on the six main CYP450 isoforms (1A2, 2C9, 2C19, 2D6, 2E1, and 3A) were investigated both in vivo and in vitro. We monitored the body weight, survival proportions, liver index, changes in pathology, and biochemical index upon TP administration, in vivo...
January 5, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28052106/a-prediction-algorithm-for-drug-response-in-patients-with-mesial-temporal-lobe-epilepsy-based-on-clinical-and-genetic-information
#11
Mariana S Silva-Alves, Rodrigo Secolin, Benilton S Carvalho, Clarissa L Yasuda, Elizabeth Bilevicius, Marina K M Alvim, Renato O Santos, Claudia V Maurer-Morelli, Fernando Cendes, Iscia Lopes-Cendes
Mesial temporal lobe epilepsy is the most common form of adult epilepsy in surgical series. Currently, the only characteristic used to predict poor response to clinical treatment in this syndrome is the presence of hippocampal sclerosis. Single nucleotide polymorphisms (SNPs) located in genes encoding drug transporter and metabolism proteins could influence response to therapy. Therefore, we aimed to evaluate whether combining information from clinical variables as well as SNPs in candidate genes could improve the accuracy of predicting response to drug therapy in patients with mesial temporal lobe epilepsy...
2017: PloS One
https://www.readbyqxmd.com/read/28046094/analysis-of-genetic-variation-in-cyp450-genes-for-clinical-implementation
#12
Liuh Ling Goh, Chia Wei Lim, Wey Cheng Sim, Li Xian Toh, Khai Pang Leong
BACKGROUND: Genetic determinants of drug response remain stable throughout life and offer great promise to patient-tailored drug therapy. The adoption of pharmacogenetic (PGx) testing in patient care requires accurate, cost effective and rapid genotyping with clear guidance on the use of the results. Hence, we evaluated a 32 SNPs panel for implementing PGx testing in clinical laboratories. METHODS: We designed a 32-SNP panel for PGx testing in clinical laboratories...
2017: PloS One
https://www.readbyqxmd.com/read/28032016/rapid-naked-eye-discrimination-of-cytochrome-p450-genetic-polymorphism-through-non-crosslinking-aggregation-of-dna-functionalized-gold-nanoparticles
#13
Yoshitsugu Akiyama, Guoqing Wang, Shota Shiraishi, Naoki Kanayama, Tohru Takarada, Mizuo Maeda
Involvement of single-nucleotide polymorphism (SNP) genotyping in healthcare should allow for more effective use of pharmacogenomics. However, user-friendly assays without the requirement of a special instrument still remain unavailable. This study describes naked-eye SNP discrimination in exon 5 of the human cytochrome P450 2C19 monooxygenase gene, CYP2C19*1 (the wild-type allele) and CYP2C19*2 (the variant allele with G681A point mutation). The present assay is composed of allele-specific single-base primer extension and salt-induced aggregation of DNA-modified gold nanoparticles (DNA-AuNPs)...
December 2016: ChemistryOpen
https://www.readbyqxmd.com/read/28025947/genetics-in-the-clinical-decision-of-antiplatelet-treatment
#14
Gerasimos Siasos, Marina Zaromitidou, Evangelos Oikonomou, Manolis Vavuranakis, Vicky Tsigkou, Nikolaos Papageorgiou, Dimitrios Chaniotis, Dimitrios A Vrachatis, Christodoulos Stefanadis, Athanasios G Papavassiliou, Dimitrios Tousoulis
BACKGROUND: Coronary artery disease remains the leading cause of death globally. Dual antiplatelet treatment with aspirin and aP2Y12 receptor significantly reduces thrombotic events. However, antiplatelet drug response displays considerable interindividual variability. METHODS: Genetic factors account for up to 70% of impaired drug response. A number of genes encoding proteins involved in the pharmacokinetic pathway have been found to alter drug response. RESULTS: According to most studies, CYP2C19 gene is the strongest genetic determinant...
December 26, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28024166/an-east-asian-perspective-on-the-interaction-between-proton-pump-inhibitors-and-clopidogrel
#15
Duowu Zou, Khean-Lee Goh
Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against aspirin gastropathy and for ARDs (Acid Related Disorders) including gastroesophageal reflux disease (GERD). They are also co-prescribed with oral anticoagulant agents (OAAs)and with dual-antiplatelet therapy (DAPT) for the treatment and prevention of gastrointestinal (GI) bleeding. Clopidogrel belongs to the drug class of thienopyridines, and is currently the most widely prescribed OAA either alone or in combination with aspirin...
December 26, 2016: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28007398/development-of-gc-ms-based-cytochrome-p450-assay-for-the-investigation-of-multi-herb-interaction
#16
Hyun-A Oh, Hyunbeom Lee, Donghak Kim, Byung Hwa Jung
As drug interactions with cytochrome P450 enzymes become increasingly important in the field of drug discovery, a high-throughput screening method for analysing the effects of a drug is needed. We have developed a simple and rapid simultaneous analytical method using a cocktail approach for measuring the activities of seven cytochrome P450 enzymes (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4). Human liver microsomes were used as a source for the seven cytochrome P450 enzymes, and a gas chromatography-mass spectrometry (GC-MS) was used for analysing their activities...
February 15, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28004391/should-race-genotype-interactions-be-considered-in-the-global-development-of-cyp2c19-substrates-a-proposed-framework-using-physiologically-based-pharmacokinetic-modeling
#17
Chirag Patel, Chetan Rathi, Karthik Venkatakrishnan
No abstract text is available yet for this article.
December 22, 2016: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28004284/a-phase-i-study-of-tivantinib-in-combination-with-temsirolimus-in-patients-with-advanced-solid-tumors
#18
Christos E Kyriakopoulos, Amy M Braden, Jill M Kolesar, Jens C Eickhoff, Howard H Bailey, Jennifer Heideman, Glenn Liu, Kari B Wisinski
Background A wide variety of human cancers exhibit dysregulated c-Met activity that has implications in oncogenesis. Phosphorylation of c-Met results in activation of the PI3K/AKT/mTOR pathway. Combined blockade of c-Met and mTOR pathways has shown efficacy in preclinical studies. Tivantinib is a c-Met inhibitor and temsirolimus is a selective mTOR inhibitor. We aimed to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D), dose-limiting toxicities (DLT), adverse events (AEs), clinical activity and pharmacokinetic (PK) parameters of the combination...
December 21, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27997040/clinical-pharmacogenetics-implementation-consortium-guideline-cpic%C3%A2-for-cyp2d6-and-cyp2c19-genotypes-and-dosing-of-tricyclic-antidepressants-2016-update
#19
J Kevin Hicks, Katrin Sangkuhl, Jesse J Swen, Vicki L Ellingrod, Daniel J Müller, Kazutaka Shimoda, Jeffrey R Bishop, Evan D Kharasch, Todd C Skaar, Andrea Gaedigk, Henry M Dunnenberger, Teri E Klein, Kelly E Caudle, Julia C Stingl
CYP2D6 and CYP2C19 polymorphisms affect the exposure, efficacy and safety of tricyclic antidepressants (TCAs), with some drugs being affected by CYP2D6 only (e.g., nortriptyline and desipramine) and others by both polymorphic enzymes (e.g., amitriptyline, clomipramine, doxepin, imipramine, and trimipramine). Evidence is presented for CYP2D6 and CYP2C19 genotype-directed dosing of TCAs. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants...
December 20, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27991432/the-effect-of-proton-pump-inhibitors-on-the-cyp2c19-enzyme-activity-evaluated-by-the-pantoprazole-13-c-breath-test-in-gerd-patients-clinical-relevance-for-personalized-medicine
#20
Anil S Modak, Iryna Klyarytska, Valerij Kriviy, Tatjana Tsapyak, Yliya Rabotyagova
Patients with gastroesophageal reflux disease (GERD) are routinely prescribed one of the six FDA approved proton pump inhibitors (PPI). All of these PPI are inhibitors of CYP2C19 enzyme to varying degrees. The phenotype pantoprazole-(13)C breath test (Ptz-BT) was used to identify patients who are poor metabolizers (PM) and the extent of phenoconversion of CYP2C19 enzyme activity caused by four PPI (omeprazole, esomprazole pantoprazole and rabeprazole) in 54 newly diagnosed GERD patients prior to initiating randomly selected PPI therapy and 30 d after PPI therapy...
December 17, 2016: Journal of Breath Research
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