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https://www.readbyqxmd.com/read/29782255/-high-on-treatment-platelet-reactivity-determinants-on-dual-antiplatelet-therapy-in-patients-with-ischemic-heart-disease-before-elective-percutaneous-coronary-intervention
#1
E Z Golukhova, M V Grigoryan, M N Ryabinina, N I Bulaeva
OBJECTIVE: to determine impact of different laboratory and genetic factors on high on-treatment platelet reactivity (HOPR) during dual antiplatelet therapy (DAPT). METHODS: We included in this study 94 patients with stable ischemic heart disease (mean age 59±9.67 years). All patients underwent elective PCI with implantation of drug eluting stents at the background of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Platelet reactivity was assessed using light transmission aggregometry with 5 μmol/L ADP (LTA 5ADP) and VerifyNow assay before PCI...
April 2018: Kardiologiia
https://www.readbyqxmd.com/read/29780235/the-cytochrome-p450-isoenzyme-and-some-new-opportunities-for-the-prediction-of-negative-drug-interaction-in-vivo
#2
REVIEW
Dmitrij A Sychev, Ghulam Md Ashraf, Andrey A Svistunov, Maksim L Maksimov, Vadim V Tarasov, Vladimir N Chubarev, Vitalij A Otdelenov, Natal'ja P Denisenko, George E Barreto, Gjumrakch Aliev
Cytochrome (CYP) 450 isoenzymes are the basic enzymes involved in Phase I biotransformation. The most important role in biotransformation belongs to CYP3A4, CYP2D6, CYP2C9, CYP2C19 and CYP1A2. Inhibition and induction of CYP isoenzymes caused by drugs are important and clinically relevant pharmacokinetic mechanisms of drug interaction. Investigation of the activity of CYP isoenzymes by using phenotyping methods (such as the determination of the concentration of specific substrates and metabolites in biological fluids) during drug administration provides the prediction of negative side effects caused by drug interaction...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29779438/metabolism-of-deltamethrin-and-cis-and-trans-permethrin-by-human-expressed-cytochrome-p450-and-carboxylesterase-enzymes
#3
Laura Hedges, Susan Brown, A Kenneth MacLeod, Audrey Vardy, Edward Doyle, Gina Song, Marjory Moreau, Miyoung Yoon, Thomas G Osimitz, Brian G Lake
1. The metabolism of the pyrethroids deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes. 2. DLM, CPM and TPM were metabolised by human CYP2B6 and CYP2C19, with the highest apparent intrinsic clearance (CLint ) values for pyrethroid metabolism being observed with CYP2C19. Other CYP enzymes contributing to the metabolism of one or more of the three pyrethroids were CYP1A2, CYP2C8, CYP2C9*1, CYP2D6*1, CYP3A4 and CYP3A5...
May 21, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29777729/pharmacogenetic-tests-to-guide-drug-treatment-in-depression-comparison-of-the-available-testing-kits-and-clinical-trials
#4
REVIEW
Chiara Fabbri, Joseph Zohar, Alessandro Serretti
The empirical approach to drug choice and dosing in depression often results into inadequate response and side effects. Pharmacogenetic (PGx) testing appears a promising way to implement personalized treatments. A systematic review was performed to identify available PGx tests, compare the genes they include with clinical guidelines and drug labels, and assess the quality of published clinical studies. ~40 commercial PGx tests are available and potential benefits were estimated for nine of them by clinical studies...
May 16, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29777510/clopidogrel-pharmacogenetics-in-iranian-patients-undergoing-percutaneous-coronary-intervention
#5
Nejat Mahdieh, Ahmad Rabbani, Ata Firouzi, Ali Zahedmehr, Maryam Hoseinimoghaddam, Sedigheh Saeidi, Hamidreza Sanati, Hosseinali Basiri, Feridoun Noohi, Bahareh Rabbani, Majid Maleki
Clopidogrel is used in patients with coronary syndromes and at risk of thrombotic events or receiving percutaneous coronary intervention (PCI) for reducing heart attack and stroke. Here we present genotype and phenotype study of Iranian patients undergoing PCI treated with clopidogrel during a 6-month period of follow-up; common variants of CYP2C19, CYP3A5, CYP3A4, and ABCB1 genes were determined as well as the patients' cardiovascular outcomes to find out the effect of these variants individually and in combination...
May 18, 2018: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29774574/nonsynonymous-single-nucleotide-polymorphisms-in-candidate-genes-p2ry1-p2ry12-and-cyp2c19-for-clopidogrel-efficacy-in-cats
#6
Yu Ueda, Ronald Hak Long Li, Fern Tablin, Eric S Ontiveros, Joshua A Stern
No abstract text is available yet for this article.
May 18, 2018: Animal Genetics
https://www.readbyqxmd.com/read/29774122/the-down-regulation-of-the-cyp2c19-gene-is-associated-with-aggressive-tumor-potential-and-the-poorer-recurrence-free-survival-of-hepatocellular-carcinoma
#7
Ryo Ashida, Yukiyasu Okamura, Keiichi Ohshima, Yuko Kakuda, Katsuhiko Uesaka, Teiichi Sugiura, Takaaki Ito, Yusuke Yamamoto, Takashi Sugino, Kenichi Urakami, Masatoshi Kusuhara, Ken Yamaguchi
Project HOPE (High-tech Omics-based Patient Evaluation) began in 2014 using integrated gene expression profiling (GEP) of cancer tissues as well as diathesis of each patient who underwent an operation at our institution. The aim of this study was to clarify the association between the expression of cytochrome P450s (CYP) genes and recurrence of hepatocellular carcinoma (HCC). The present study included 92 patients. Genes with aberrant expression were selected based on a ≥10-fold difference in the expression between tumor and non-tumor tissues...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29768302/pharmacogenomics-in-papua-new-guineans-unique-profiles-and-implications-for-enhancing-drug-efficacy-while-improving-drug-safety
#8
Joseph D Tucci, Paul P Pumuye, Nuala A Helsby, Daniel T Barratt, Percy P Pokeya, Francis Hombhanje, Andrew A Somogyi
Papua New Guinea (PNG) can be roughly divided into highland, coastal and island peoples with significant mitochondrial DNA differentiation reflecting early and recent distinct migrations from Africa and East Asia, respectively. Infectious diseases such as tuberculosis, malaria and HIV severely impact on the health of its peoples for which drug therapy is the major treatment and pharmacogenetics has clinical relevance for many of these drugs. Although there is generally little information about known single nucleotide polymorphisms in the population, in some instances, their frequencies have been shown to be higher than anywhere worldwide...
June 2018: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/29762875/in-vivo-assessment-of-the-effect-of-cyp1a2-inhibition-and-induction-on-pomalidomide-pharmacokinetics-in-healthy-subjects
#9
Yan Li, Liangang Liu, Xiaomin Wang, Chengyue Zhang, Josephine Reyes, Matthew Hoffmann, Maria Palmisano, Simon Zhou
Pomalidomide is an immunomodulatory drug, and the dosage of 4 mg per day taken orally on days 1-21 of repeated 28-day cycles has been approved in the European Union and the United States to treat patients with relapsed/refractory multiple myeloma. In vitro data showed that pomalidomide is a substrate of multiple cytochrome P450 (CYP) isozymes and that its oxidative metabolism is mediated primarily by CYP1A2 and CYP3A4, with minor contributions from CYP2C19 and CYP2D6. The effect of CYP1A2 inhibition by fluvoxamine (a strong CYP1A2 inhibitor) and CYP1A2 induction by smoking on pomalidomide pharmacokinetics in healthy subjects has been assessed in 2 separate phase 1 open-label, single-dose studies...
May 15, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29756345/common-polymorphisms-of-cyp2b6-influence-stereoselective-bupropion-disposition
#10
Evan D Kharasch, Amanda Crafford
Bupropion hydroxylation is a bioactivation and metabolic pathway, and the standard clinical CYP2B6 probe. This investigation determined the influence of CYP2B6 allelic variants on clinical concentrations and metabolism of bupropion enantiomers. Secondary objectives evaluated the influence of CYP2C19 and P450 oxidoreductase variants. Healthy volunteers in specific cohorts (CYP2B6*1/*1, CYP2B6*1/*6, CYP2B6*6/*6, and also CYP2B6*4 carriers) received single-dose oral bupropion. Plasma and urine bupropion and hydroxybupropion was quantified...
May 14, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29749249/hplc-high-resolution-mass-spectrometry-with-polarity-switching-for-increasing-throughput-of-human-in-vitro-cocktail-drug-drug-interaction-assay
#11
Ragu Ramanathan, Anima Ghosal, Lakshmi Ramanathan, Kate Comstock, Helen Shen, Dil Ramanathan
AIM: Evaluation of HPLC-high-resolution mass spectrometry (HPLC-HRMS) full scan with polarity switching for increasing throughput of human in vitro cocktail drug-drug interaction assay. MATERIALS & METHODS: Microsomal incubates were analyzed using a high resolution and high mass accuracy Q-Exactive mass spectrometer to collect integrated qualitative and quantitative (Qual/Quant) data. RESULTS: Within assay, positive-to-negative polarity switching HPLC-HRMS method allowed quantification of eight and two probe compounds in the positive and negative ionization modes, respectively, while monitoring for LOR and its metabolites...
May 11, 2018: Bioanalysis
https://www.readbyqxmd.com/read/29746397/impact-of-drug-interactions-on-clobazam-and-n-desmethylclobazam-concentrations-in-pediatric-patients-with-epilepsy
#12
Gabrielle R Russell, Stephanie J Phelps, Chasity M Shelton, James W Wheless
BACKGROUND: Clobazam (CLB) is approved as adjunctive treatment for seizures associated with Lennox-Gastaut syndrome in patients ≥2 years of age. It is converted to an active metabolite N-desmethylclobazam (NCLB) by CYP3A4, which is then broken down to an inactive metabolite by CYP2C19. This study characterizes the impact of CYP3A4 and CYP2C19 drug interactions on CLB and NCLB serum concentrations (Cp) and concentration/dose (Cp/D) ratios in pediatric patients with epilepsy. METHODS: This was a retrospective chart review including patients >1 month of age, who received CLB between April 2012 and March 2017...
May 4, 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29743380/tailored-adjunctive-cilostazol-therapy-based-on-cyp2c19-genotyping-in-patients-with-acute-myocardial-infarction-the-caldera-gene-study
#13
Koichi Kaikita, Hiromi Yoshimura, Masanobu Ishii, Takashi Kudoh, Yoshihiro Yamada, Eiichiro Yamamoto, Yasuhiro Izumiya, Sunao Kojima, Hideki Shimomura, Ryusuke Tsunoda, Kunihiko Matsui, Hisao Ogawa, Kenichi Tsujita
BACKGROUND: Patients with reduced-function CYP2C19 genotypes on dual antiplatelet therapy (DAPT) with aspirin and clopidogrel show higher clinical risk for acute myocardial infarction (AMI). We investigated the effect of CYP2C19 genotype-tailored adjunctive cilostazol therapy on treatment of AMI.Methods and Results:The study group of 138 patients with suspected AMI were screened for CYP2C19 genotype immediately after percutaneous coronary intervention (PCI) using a SPARTAN RX point-of-care device...
May 8, 2018: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/29741901/stereoselective-metabolism-of-omeprazole-by-cytochrome-p-450-2c19-and-3a4-mechanistic-insights-from-dft-study
#14
Kalyanashis Jana, Tusar Bandyopadhyay, Bishwajit Ganguly
The efficacy of S-omeprazole as proton pump inhibitor compared to its enantiomer R-omeprazole is studied using density functional theoretical calculations. The pharmacokinetic studies suggest that the efficacy of S-omeprazole presumably depends on metabolic pathway and excretion from the human body. The DFT calculations at SMDWater -B3LYP-D3/6-311+G(d,p)/LANL2DZ//B3LYP/6-31G(d)/LANL2DZ with triradicaloid model active species, [Por•+ FeIV (SH)O], of the CYP2C19 enzyme with high spin quartet and low spin doublet states demonstrate C-H bond activation mechanism through a two-state rebound process for hydroxylation of R-omeprazole and S-omeprazole...
May 9, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29738669/cypreact-a-software-tool-for-in-silico-reactant-prediction-for-human-cytochrome-p450-enzymes
#15
Siyang Tian, Yannick Djoumbou, Russ Greiner, David S Wishart
In silico metabolism prediction requires first predicting whether a specific molecule will interact with one or more specific metabolizing enzymes, then predicting the result of each enzymatic reaction. Here, we provide a computational tool, CypReact, for performing this first task of reactant prediction. Specically, CypReact takes as input an arbitrary molecule (specied as a SMILES string or a standard SDF file), and any one of the nine of the most important human cytochrome P450 (CYP450) enzymes -- CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4 -- and accurately predicts whether the query molecule will react with that given CYP450 enzyme...
May 8, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29738309/pharmacogenetic-testing-by-polymorphic-markers-681g-a-and-636g-a-cyp2c19-gene-in-patients-with-acute-coronary-syndrome-and-gastric-ulcer-in-the-republic-of-sakha-yakutia
#16
Denis S Fedorinov, Karin B Mirzaev, Dmitriy V Ivashchenko, Ilyas I Temirbulatov, Dmitriy A Sychev, Nadezda R Maksimova, Jana V Chertovskih, Nyurguiana V Popova, Ksenia S Tayurskaya, Zoya A Rudykh
BACKGROUND: The focus of the study is to determine the prevalence of CYP2C19 alleles, associated with the risk of changes in the pharmacological response to clopidogrel and proton pump inhibitors in patients with acute coronary syndrome (ACS) and gastric ulcer from Russian and Yakut ethnic groups. METHODS: The research included 411 patients with ACS (143 Russians and 268 Yakuts) and 204 patients with histologically confirmed gastric ulcer (63 Russians and 141 Yakuts)...
May 8, 2018: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/29735754/an-assessment-of-the-in-vitro-inhibition-of-cytochrome-p450-enzymes-cyp-udp-glucuronsyltransferases-ugt-and-transporters-by-phosphodiester-or-phosphorothioate-linked-oligonucleotides
#17
Faraz Kazmi, Phyllis Yerino, Chase McCoy, Andrew Parkinson, David B Buckley, Brian W Ogilvie
Oligonucleotides represent an expanding class of pharmacotherapeutics in development for various indications. Typically, oligonucleotides are developed with phosphorothioate linkages for the improvement of biological stability; however limited data are available on the potential of these molecules to cause drug-drug interactions (DDIs). In the present study, two non therapeutic oligonucleotides with either phosphodiester (PD-GP and PD-Ac) or phosphorothioate (PT-GP and PT-Ac) linkages were evaluated in vitro for their potential to inhibit P450s and UGTs in both human liver microsomes (HLM) and cryopreserved human hepatocytes (CHH) and to inhibit select transporters in expression systems...
May 7, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29733119/correspondence-between-the-cyp2c19-and-cyp3a4-genotypes-with-the-inferred-metabolizer-phenotype-by-omeprazole-administration-in-mexican-healthy-children
#18
A F Favela-Mendoza, G Martínez-Cortes, M M Romero-Prado, E M Romero-Tejeda, M C Islas-Carbajal, M Sosa-Macias, I Lares-Asseff, H Rangel-Villalobos
WHAT IS KNOWN AND OBJECTIVE: CYP2C19 genotypes presumably allow the prediction of the metabolizer phenotypes: poor (PMs), extensive (EMs) and ultra-rapid (UMs). However, evidence from previous studies regarding this predictive power is unclear, which is important because the benefits expected by healthcare institutions and patients are based on this premise. Therefore, we aimed to complete a formal evaluation of the diagnostic value of CYP2C19 and CYP3A4 genes for predicting metabolizer phenotypes established by omeprazole (OME) administration in 118 healthy children from Jalisco (western Mexico)...
May 7, 2018: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29727298/which-cytochrome-p450-metabolizes-phenazepam-step-by-step-in-silico-in-vitro-and-in-vivo-studies
#19
Dmitriy V Ivashchenko, Anastasia V Rudik, Andrey A Poloznikov, Sergey V Nikulin, Valeriy V Smirnov, Alexander G Tonevitsky, Eugeniy A Bryun, Dmitriy A Sychev
BACKGROUND: Phenazepam (bromdihydrochlorphenylbenzodiazepine) is the original Russian benzodiazepine tranquilizer belonging to 1,4-benzodiazepines. There is still limited knowledge about phenazepam's metabolic liver pathways and other pharmacokinetic features. METHODS: To determine phenazepam's metabolic pathways, the study was divided into three stages: in silico modeling, in vitro experiment (cell culture study), and in vivo confirmation. In silico modeling was performed on the specialized software PASS and GUSAR to evaluate phenazepam molecule affinity to different cytochromes...
May 4, 2018: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/29723426/cyp2c19-or-cyp3a5-genotyping-does-not-predict-clinical-response-to-clopidogrel
#20
Fayna Rodríguez-González, Efren Martínez-Quintana, Pedro Saavedra, José M Medina-Gil, Marta Riaño, Paloma Garay-Sánchez, Antonio Tugores
Along with aspirin, clopidogrel has been a widely used antiplatelet therapeutic regimen. Although generally well tolerated, its efficacy varies among individuals, with the main hypothesis that its bioavailability relies on its bioconversion to the active compound, which, in turn, depends on the genetic background and/or interactions with other drugs. To determine which factors influenced response in our patients, 368 patients receiving combined antiaggregation therapy with aspirin and clopidogrel were followed for 1 year to record 30 novel cardiovascular acute events...
May 3, 2018: Journal of Clinical Pharmacology
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