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https://www.readbyqxmd.com/read/28817838/pharmacogenetic-determinants-of-outcomes-on-triplet-hepatic-artery-infusion-and-intravenous-cetuximab-for-liver-metastases-from-colorectal-cancer-european-trial-optiliv-nct00852228
#1
Francis Lévi, Abdoulaye Karaboué, Raphaël Saffroy, Christophe Desterke, Valerie Boige, Denis Smith, Mohamed Hebbar, Pasquale Innominato, Julien Taieb, Carlos Carvalho, Rosine Guimbaud, Christian Focan, Mohamed Bouchahda, René Adam, Michel Ducreux, Gérard Milano, Antoinette Lemoine
BACKGROUND: The hepatic artery infusion (HAI) of irinotecan, oxaliplatin and 5-fluorouracil with intravenous cetuximab achieved outstanding efficacy in previously treated patients with initially unresectable liver metastases from colorectal cancer. This planned study aimed at the identification of pharmacogenetic predictors of outcomes. METHODS: Circulating mononuclear cells were analysed for 207 single-nucleotide polymorphisms (SNPs) from 34 pharmacology genes...
August 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28817535/can-prasugrel-decrease-the-extent-of-periprocedural-myocardial-injury-during-elective-pci
#2
Mariusz Tomaniak, Łukasz Kołtowski, Janusz Kochman, Zenon Huczek, Adam Rdzanek, Arkadiusz Pietrasik, Aleksandra Gasecka, Sylwia Gajda, Grzegorz Opolski, Krzysztof J Filipiak
INTRODUCTION    Periprocedural myocardial injury may be associated with an increased risk of cardiovascular events. The evidence on safety and efficacy of more potent P2Y12 antagonists in reduction of periprocedural myocardial injury among patients undergoing elective percutaneous coronary interventions (PCI) with inadequate response to clopidogrel is limited.  OBJECTIVES    The aim of the study was to evaluate the impact of prasugrel on the incidence of periprocedural myocardial injury among patients undergoing elective PCI with inadequate response to clopidogrel diagnosed by point-of-care genotyping and platelet function testing (PFT)...
August 17, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28810096/point-counterpoint-cyp2c19-genotyping-for-clopidogrel
#3
Eric A Larson, Nathan J Miller
No abstract text is available yet for this article.
January 2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28808886/assessment-of-pharmacokinetic-interactions-between-obeticholic-acid-and-caffeine-midazolam-warfarin-dextromethorphan-omeprazole-rosuvastatin-and-digoxin-in-phase-1-studies-in-healthy-subjects
#4
Jeffrey E Edwards, Lise Eliot, Andrew Parkinson, Sharon Karan, Leigh MacConell
INTRODUCTION: Obeticholic acid (OCA), a potent and selective farnesoid X receptor agonist, is indicated for the treatment of primary biliary cholangitis (PBC). We investigated the potential drug-drug interaction effect of OCA on metabolic CYP450 enzymes and drug transporters. METHODS: Five phase 1 single-center, open-label, fixed-sequence, inpatient studies were conducted in healthy adult subjects to evaluate the effect of oral daily doses of 10 or 25 mg OCA on single-dose plasma pharmacokinetics of specific probe substrates for enzymes CYP1A2 (caffeine, R-warfarin), CYP3A (midazolam, R-warfarin), CYP2C9 (S-warfarin), CYP2D6 (dextromethorphan), CYP2C19 (omeprazole), and drug transporters, BCRP/OATP1B1/OATP1B3 (rosuvastatin), and P-gp (digoxin)...
August 14, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28808507/cyp2c19-genetic-variation-and-individualized-clopidogrel-prescription-in-a-cardiology-clinic
#5
Seyed Abbas Mirabbasi, Koroush Khalighi, Yin Wu, Stanley Walker, Bahar Khalighi, Wuqiang Fan, Archana Kodali, Gang Cheng
Background: Clopidogrel (Plavix) is an antiplatelet medication that is routinely used in patients with cardiovascular disease. Cytochrome P2C19 enzymes play a major role in its metabolism, which determines its varied therapeutic level and its effectiveness. Objectives: To customize clopidogrel therapy and evaluate its efficacy by using CYP2C19 genotypic and phenotypic information to improve clinical outcomes in patients. Methods: A total of 465 patients with underlying cardiovascular disease were selected from our out-patient cardiology clinic...
July 2017: Journal of Community Hospital Internal Medicine Perspectives
https://www.readbyqxmd.com/read/28806186/the-impact-of-cyp2c19-2-cyp4f2-3-and-clinical-factors-on-platelet-aggregation-cyp4f2-enzyme-activity-and-20-hydroxyeicosatetraenoic-acid-concentration-in-patients-treated-with-dual-antiplatelet-therapy
#6
Vacis Tatarunas, Nora Kupstyte, Agne Giedraitiene, Vilius Skipskis, Valdas Jakstas, Vaidotas Zvikas, Vaiva Lesauskaite
: The aim of the current study was to evaluate the impact of CYP2C192 (rs4244285), CYP4F23 (rs2108622), and nongenetic factors on platelet aggregation and to investigate the mechanism of CYP4F2's effect on platelet aggregation in the patients treated with dual antiplatelet therapy. A total of 146 patients were included in this study. Ticagrelor or clopidogrel were administered in a loading dose of 180 mg and 600 mg, respectively, in combination with aspirin (300 mg). Blood samples for analysis were taken the next morning after antiplatelet therapy induction...
August 12, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28798474/cyp2c19-2-and-cyp2c19-17-variants-and-effect-of-tamoxifen-on-breast-cancer-recurrence-analysis-of-the-international-tamoxifen-pharmacogenomics-consortium-dataset
#7
Per Damkier, Anders Kjærsgaard, Kimberly A Barker, Deidre Cronin-Fenton, Anatasha Crawford, Ylva Hellberg, Emilius A M Janssen, Carl Langefeld, Thomas P Ahern, Timothy L Lash
The role of cytochrome P450 drug metabolizing enzymes in the efficacy of tamoxifen treatment of breast cancer is subject to substantial interest and controversy. CYP2D6 have been intensively studied, but the role of CYP2C19 is less elucidated, and we studied the association of CYPC19 genotype and recurrence of breast cancer. We used outcome and genotyping data from the large publicly available International Tamoxifen Pharmacogenomics Consortium (ITPC) dataset. Cox regression was used to compute the hazard ratios (HRs) for recurrence...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28792790/recent-developments-and-future-directions-for-the-use-of-pharmacogenomics-in-cardiovascular-disease-treatments
#8
Andrew Levy, Elliot Berinstein
Cardiovascular disease is still the leading cause of death worldwide. There are many environmental and genetic factors that play a role in the development of cardiovascular disease. The treatment of cardiovascular disease is beginning to move in the direction of personalized medicine by using biomarkers from patient's genome to design more effective treatment plans. Pharmacogenomics have already uncovered many links between genetic variation and response of many different drugs. Areas covered: This article will focus on the main polymorphisms that impact the risk of adverse effects and response efficacy of statins, clopidogrel, aspirin, β-blockers, warfarin dalcetrapib and vitamin E...
August 9, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28783717/effects-of-dual-dose-clopidogrel-clopidogrel-combined-with-tongxinluo-capsule-and-ticagrelor-on-patients-with-coronary-heart-disease-and-cyp2c19-2-gene-mutation-after-percutaneous-coronary-interventions-pci
#9
Shuxia Chen, Yi Zhang, Lili Wang, Yanping Geng, Jian Gu, Qingqing Hao, Hua Wang, Peng Qi
BACKGROUND In recent years, genetic factors have attracted research interest as important predisposing factors for cardiovascular susceptibility. This study aimed to investigate the influences of dual-dose clopidogrel, clopidogrel combined with tongxinluo, and ticagrelor on the platelet activity and MACE events of patients with CYP2C19*2 gene function deficiency and poor clopidogrel response after PCI. MATERIAL AND METHODS We selected 458 patients with coronary heart disease undergoing PCI, and the genotype of CYP2C19*2 was detected by TaqMan real-time PCR...
August 7, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28777243/systematic-evaluation-of-commercial-pharmacogenetic-testing-in-psychiatry-a-focus-on-cyp2d6-and-cyp2c19-allele-coverage-and-results-reporting
#10
Chad A Bousman, Philip Jaksa, Christos Pantelis
OBJECTIVE: The aim of this study was to systematically assess commercial pharmacogenetic tests relevant to prescribing in psychiatry, with specific attention on CYP2D6 and CYP2C19 star allele coverage as well as compliance with consensus recommendations for pharmacogenetic test result reporting. MATERIALS AND METHODS: The CYP2D6 and CY2C19 star (*) allele contents of 20 pharmacogenetic test panels were compared and their test results reports were evaluated on the basis of consensus reporting recommendations published by The Centers for Disease Control and Prevention as well as the Clinical Pharmacogenetics Implementation Consortium...
August 2, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28776468/falls-the-adverse-drug-reaction-of-the-elderly-and-the-impact-of-pharmacogenetics
#11
Katja Susanne Just, Katharina Luise Schneider, Marlen Schurig, Julia Carolin Stingl, Jürgen Brockmöller
Falls is a frequent type of adverse drug reactions causing significant morbidity and mortality in the elderly. We reviewed, with which drugs the risk of falls is relevant and might depend on genomic variation. Pharmacogenetic variability may contribute to drug-induced falls for instance mediated by impaired drug elimination due to inherited deficiency in enzymes like CYP2C9, CYP2C19 and CYP2D6. The relative role of specific genes and polymorphisms in old age may differ from younger people. Biomarkers for frailty, but also genomic biomarkers might help identifying patients at high risk for drug-induced falls...
August 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28774812/cytochrome-p450-inhibition-by-three-licorice-species-and-fourteen-licorice-constituents
#12
Guannan Li, Charlotte Simmler, Luying Chen, Dejan Nikolic, Shao-Nong Chen, Guido F Pauli, Richard B van Breemen
The potential of licorice dietary supplements to interact with drug metabolism was evaluated by testing extracts of three botanically identified licorice species (Glycyrrhiza glabra L., Glycyrrhiza uralensis Fish. ex DC. and Glycyrrhiza inflata Batalin) and 14 isolated licorice compounds for inhibition of 9 cytochrome P450 enzymes using a UHPLC-MS/MS cocktail assay. G. glabra showed moderate inhibitory effects against CYP2B6, CYP2C8, CYP2C9, and CYP2C19, and weak inhibition against CYP3A4 (testosterone). In contrast, G...
July 31, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28766499/association-between-platelet-function-and-recurrent-ischemic-vascular-events-after-tia%C3%A2-and-minor-stroke%C3%A2
#13
Jinbiao Zhang, Jiangshan Zhang, Hairong Sun, Tan Ming, Xinwu Liu, Yannan Cong, Fang Li, Zhenguang Li
Platelet activation and aggregation play an important role in the pathological and physiological processes of recurrent ischemic vascular events in stroke patients. The purpose of this study is to determine the association between platelet function measured in the acute period and recurrent ischemic vascular events in patients with transient ischemic attack (TIA) or minor stroke. A total of 417 patients who were within the 24-hour period of clopidogrel-aspirin therapy after onset of a minor stroke or high-risk transient ischemic attack according to the Clopidogrel in High-risk patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial were included in this study...
August 2, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28762043/customised-in-vitro-model-to-detect-human-metabolism-dependent-idiosyncratic-drug-induced-liver-injury
#14
Laia Tolosa, Nuria Jiménez, Gabriela Pérez, José V Castell, M José Gómez-Lechón, M Teresa Donato
Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify metabolic phenotypes with increased susceptibility to DILI...
July 31, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28756170/confirmation-of-metabolites-of-the-neuroleptic-drug-prothipendyl-using-human-liver-microsomes-specific-cyp-enzymes-and-authentic-forensic-samples-benefit-for-routine-drug-testing
#15
M Krämer, S Broecker, B Madea, C Hess
Metabolism of the tricyclic azaphenothiazine neuroleptic drug prothipendyl was investigated with in vitro studies using human liver microsomes but also specific isoforms of cytochrome P450 (CYP) enzymes. Identification and analysis of metabolites was done by liquid chromatography (LC) coupled with quadrupole time of flight mass spectrometry (LC-QTOF-MS) as well as triple quadrupole mass spectrometry (LC-QQQ-MS). Results of the herein presented study revealed the proof of various demethylated and oxidized metabolites (-CH2, -C2H4, four derivatives of prothipendyl +O and three derivatives of prothipendyl -CH2+O)...
July 12, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28752932/development-of-genotyping-method-for-functionally-relevant-variants-of-cytochromes-p450-in-cynomolgus-macaques
#16
Y Uno, N Osada, S Sakurai, N Shimozawa, T Iwata, K Ikeo, H Yamazaki
In cynomolgus macaques (Macaca fascicularis), widely used in drug metabolism studies, CYP2C9, CYP2C76, CYP2D6, CYP3A4, and CYP3A5, important drug-metabolizing enzymes, are abundantly expressed in liver and metabolize cytochrome P450 substrates. CYP2C9 (c.334A>C), CYP2C76 (c.449TG>A), CYP2D6 (c.891A>G), CYP3A4 (IVS3 + 1G>del), and CYP3A5 (c.625A>T) substantially influence metabolic activity of enzymes, and thus are important variants in drug metabolism studies. In this study, a real-time PCR method was developed for genotyping these variants...
July 28, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28752728/evaluation-of-on-clopidogrel-platelet-reactivity-overtime-syntax-score-genetic-polymorphisms-and-their-relationship-to-one-year-clinical-outcomes-in-stemi-patients-undergoing-pci
#17
Harsha V Erathi, Rajasekhar Durgaprasad, Vanajakshamma Velam, P V Sarma, Madhavi Rodda, C Kapil, Sreedhar N Kanavath
OBJECTIVES: To investigate the variability of On-clopidogrel platelet reactivity overtime, the association between HTPR, gene polymorphism and Syntax Score (SS) for risk prediction of MACE in patients with ST-Elevation Myocardial Infarction (STEMI) undergoing percutaneous coronary intervention (PCI). BACKGROUND: Platelet function testing may be used to optimize antiplatelet therapy in high risk patients, but identification of this subset of patients remains a challenge...
July 27, 2017: Minerva Cardioangiologica
https://www.readbyqxmd.com/read/28748348/impact-of-genetic-polymorphisms-on-phenytoin-pharmacokinetics-and-clinical-outcomes-in-the-middle-east-and-north-africa-region
#18
REVIEW
Renée Dagenais, Kyle John Wilby, Hazem Elewa, Mary H H Ensom
BACKGROUND: Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood. OBJECTIVES: The objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa region, and to characterize genotypic and allelic frequencies within the region for genetic polymorphisms assessed...
July 26, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28745582/cyp2c19-guided-antiplatelet-therapy-a-cost-effectiveness-analysis-of-30-day-and-1-year-outcomes-following-percutaneous-coronary-intervention
#19
Mrudula S Borse, Olivia M Dong, Melissa J Polasek, Joel F Farley, George A Stouffer, Craig R Lee
AIM: Determine whether using CYP2C19 genotype to optimize antiplatelet therapy selection is cost effective over the initial 30 days and 1-year following percutaneous coronary intervention. MATERIALS & METHODS: A cost-effectiveness analysis compared 30-day and 1-year outcomes and cost across three treatment strategies (universal clopidogrel, universal prasugrel, genotype-guided) in a hypothetical cohort. RESULTS: Base-case scenario results at 30 days indicated that the incremental cost per major cardiovascular or bleeding event avoided for genotype-guided treatment was US$8525 and US$42,198 compared with universal clopidogrel and prasugrel, respectively...
August 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28745576/association-of-cyp2c19-2-polymorphism-with-clopidogrel-response-and-1-year-major-adverse-cardiovascular-events-in-a-multiethnic-population-with-drug-eluting-stents
#20
Shirley Siang Ning Tan, Alan Yean Yip Fong, Melissa Mejin, Jerry Gerunsin, Khai Liy Kong, Felicia Yien Yin Chin, Lee Len Tiong, Melissa Siaw Han Lim, Asri Said, Ning Zan Khiew, Chi Voon Yen, Nor Hanim Mohd Amin, Yee Ling Cham, Keng Tat Koh, Yen Yee Oon, Tiong Kiam Ong
BACKGROUND: Patients undergoing elective percutaneous coronary intervention (PCI) with drug-eluting stents (DES) who have impaired clopidogrel response, have a higher risk of subsequent major adverse cardiovascular events (MACE). AIM OF THE STUDY: To establish the relationship between CYP2C19 genotype, clopidogrel responsiveness and 1-year MACE. MATERIALS & METHODS: Aspirin/clopidogrel responses were assessed with Multiplate Analyzer and CYP2C19*2 allele by SpartanRx...
July 26, 2017: Pharmacogenomics
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