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https://www.readbyqxmd.com/read/29350207/association-between-cyp2c19-and-abcb1-polymorphisms-and-clopidogrel-resistance-in-clopidogrel-treated-chinese-patients
#1
Zhong Ling Zhuo, Hai Peng Xian, Yan Long, Chang Liu, Yuan Yuan Sun, Yin Ting Ma, Hua Gao, Jing Zhong Zhao, Xiao Tao Zhao
OBJECTIVE: To investigate the association between CYP2C19 and ABCB1 polymorphisms and clopidogrel resistance (CR) in patients with cardiovascular disease in Beijing district. METHODS: In total, 325 patients were enrolled in the study, including 101 experimental group patients and 224 control group patients. The experimental group was divided into CR group (n=30) and non-CR group (n=71) according to the adenosine diphosphate (ADP)-induced platelet inhibition rate in thromboelastography (TEG) (ADP-induced platelet inhibition rate of <30% was defined as CR and rate of 30%-100% was defined as non-CR)...
January 19, 2018: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/29348104/disposition-kinetics-of-omeprazole-in-healthy-female-volunteers-in-faisalabad
#2
Sadia Ashraf, Tanweer Khaliq, Ijaz Javed, Bilal Aslam, Nazia Qadir, Nadia Noor
Omeprazole (OMP) a proton pump inhibitor is widely used to suppress gastric acid secretions of parietal cells of stomach and metabolized predominantly by CYP2C19. The objective of the present study was to investigate the pharmacokinetics and dosage regimen of OMP, after its single oral administration in eight healthy adult female subjects. Blood samples were collected at different time intervals after oral administration and their pH was measured. Plasma concentration of OMP was determined by high performance liquid chromatography (HPLC) system equipped with UV-visible Detector...
January 2018: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29347970/a-synergic-effect-between-cyp2c19-2-cyp2c19-3-loss-of-function-and-cyp2c19-17-gain-of-function-alleles-is-associated-with-clopidogrel-resistance-among-moroccan-acute-coronary-syndromes-patients
#3
Hind Hassani Idrissi, Wiam Hmimech, Nada El Khorb, Hafid Akoudad, Rachida Habbal, Sellama Nadifi
OBJECTIVE: The main objective of our study was to investigate the association of CYP2C19*2 and CYP2C19*3 loss-of-function and CYP2C19*17 gain-of-function variants of CYP2C19 gene with Clopidogrel resistance in a sample of Moroccan Acute Coronary Syndromes patients. RESULTS: Our results showed the existence of a synergic effect between the three alleles, statistically very significant, on Clopidogrel resistance among the treated patients (P = 0.0033). For the three variants of the CYP2C19 gene, the heterozygous and homozygous mutant genotypes were the most frequent among ACS patients (CYP2C19*2: 82...
January 18, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29345984/development-of-a-polymerase-chain-reaction-ligase-detection-reaction-assay-for-detection-of-cyp2c19-polymorphisms
#4
Jing Zhang, Hui Zhang, Kun Li, Ming Shi
AIMS: Cytochrome P450 2C19 (CYP2C19) genotypes are associated with differential drug metabolism. The aim of this study was to establish a reliable assay for CYP2C19 genotyping based on a polymerase chain reaction/ligase detection reaction (PCR-LDR). MATERIALS AND METHODS: Specific primers and probes were designed to detect CYP2C19*1, *2, *3, and *17. A control for each allele was prepared and used for performance evaluation. A total of 200 clinical samples were analyzed using the PCR-LDR assay and Sanger sequencing...
January 2018: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/29345044/preclinical-characterisation-of-absorption-distribution-metabolism-and-excretion-properties-of-tak-063
#5
Kimio Tohyama, Miyako Sudo, Akio Morohashi, Suguru Kato, Junzo Takahashi, Yoshihiko Tagawa
TAK-063 is currently being developed to treat schizophrenia. In this study, we investigated the absorption, distribution, metabolism and excretion (ADME) properties of TAK-063 using several paradigms. Following oral administration of TAK-063 at 0.3 mg/kg, bioavailability of TAK-063 was 27.4% in rats and 49.5% in dogs with elimination half-lives of 3.1 hr in rats and 3.7 hr in dogs. TAK-063 is a highly permeable compound without P-glycoprotein (P-gp) or breast cancer resistance protein substrate liability and can be readily absorbed into systemic circulation via the intestine...
January 17, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29335863/integrative-medicine-on-optimizing-clopidogrel-and-aspirin-therapy
#6
REVIEW
Hui Chen
This article reviews the available published data on optimizing clopidogrel and aspirin therapy using translational and integrative medicine. Translational and evidence-based medical studies show that the CYP2C19 gene mutation (CYP2C19*2 and CYP2C19*3) could affect > 50% of the Chinese population, and that this mutation is closely associated with clopidogrel resistance and an increased risk of major adverse cardiovascular events, particularly stent thrombosis in patients following percutaneous coronary intervention (PCI)...
January 15, 2018: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/29335059/association-of-%C3%AE-2a-adrenergic-receptor-genetic-variants-with-platelet-reactivity-in-chinese-patients-on-dual-antiplatelet-therapy-undergoing-percutaneous-coronary-intervention
#7
Ying Song, Xiao Fang Tang, Yi Yao, Chen He, Jing Jing Xu, Huan Huan Wang, Zhan Gao, Mia Wang, Jin Qing Yuan
OBJECTIVE: The alpha 2A-adrenergic receptor gene (ADRA2A) polymorphism in individuals modifies the antiplatelet response to sympathetic stimulation. The aim of this study was to investigate the effect of ADRA2A variants on platelet reactivity in Chinese patients on dual antiplatelet therapy (DAPT) after undergoing percutaneous coronary intervention (PCI). METHODS: From March 2011 to March 2013, 1,024 patients were enrolled in this prospective, single-center, observational study in China...
December 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/29334682/body-mass-index-and-plasma-p-selectin-before-coronary-stenting-predict-high-residual-platelet-reactivity-at-6-months-on-dual-antiplatelet-therapy
#8
Elena Z Golukhova, Marina V Grigoryan, Mariya N Ryabinina, Naida I Bulaeva, Victor L Serebruany
BACKGROUND: High residual platelet reactivity (HRPR) during dual antiplatelet therapy (DAPT) may impact clinical outcomes following percutaneous coronary interventions (PCI). However, whether any biomarkers assessed before PCI at DAPT loading may predict delayed maintenance HRPR is not clear. OBJECTIVE: The aim of this study was to determine whether conventional clinical or laboratory indices at loading before stenting may predict HRPR at 6 months of maintenance DAPT...
January 16, 2018: Cardiology
https://www.readbyqxmd.com/read/29333880/pharmacogenetic-analysis-of-opioid-dependence-treatment-dose-and-dropout-rate
#9
Richard C Crist, James Li, Glenn A Doyle, Alex Gilbert, Bryan M Dechairo, Wade H Berrettini
BACKGROUND: Currently, no pharmacogenetic tests for selecting an opioid-dependence pharmacotherapy have been approved by the US Food and Drug Administration. OBJECTIVES: Determine the effects of variants in 11 genes on dropout rate and dose in patients receiving methadone or buprenorphine/naloxone (ClinicalTrials.gov Identifier: NCT00315341). METHODS: Variants in six pharmacokinetic genes (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4) and five pharmacodynamic genes (HTR2A, OPRM1, ADRA2A, COMT, SLC6A4) were genotyped in samples from a 24-week, randomized, open-label trial of methadone and buprenorphine/naloxone for the treatment of opioid dependence (n = 764; 68...
January 15, 2018: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/29328413/prevalence-of-the-cyp2c19-2-681-g-a-3-636-g-a-and-17-%C3%A2-806-c-t-alleles-among-an-iranian-population-of-different-ethnicities
#10
Mahshid Dehbozorgi, Behnam Kamalidehghan, Iman Hosseini, Zahra Dehghanfard, Mohammad Hossein Sangtarash, Maryam Firoozi, Fatemeh Ahmadipour, Goh Yong Meng, Massoud Houshmand
Polymorphisms in the cytochrome P (CYP) 450 family may cause adverse drug responses in individuals. Cytochrome P450 2C19 (CYP2C19) is a member of the CYP family, where the presence of the 681 G>A, 636 G>A and 806 C>T polymorphisms result in the CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles, respectively. In the current study, the frequency of the CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles in an Iranian population cohort of different ethnicities were examined and then compared with previously published frequencies within other populations...
January 5, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29327975/impact-of-cyp2d6-on-venlafaxine-metabolism-in-trinidadian-patients-with-major-depressive-disorder
#11
Lazara Karelia Montané Jaime, Jeffrey Paul, Anthony Lalla, George Legall, Andrea Gaedigk
AIM: This study aimed to assess the impact of CYP2D6 and CYP2C19 variation on venlafaxine (VEN) at steady state in patients from Trinidad and Tobago of Indian and African descent with major depressive disorder. PATIENTS & METHODS: Patients were phenotyped with dextromethorphan, genotyped for CYP2D6 and CYP2C19, and metabolic ratios for VEN obtained at 2-week intervals. RESULTS: Of 61 patients, 55 were genotyped and phenotyped and 47 completed 8 weeks of VEN treatment...
January 12, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29325448/impact-of-cyp2c19-genotype-on-escitalopram-exposure-and-therapeutic-failure-a-retrospective-study-based-on-2-087-patients
#12
Marin M Jukić, Tore Haslemo, Espen Molden, Magnus Ingelman-Sundberg
OBJECTIVE: The antidepressant escitalopram is predominantly metabolized by the polymorphic CYP2C19 enzyme. The authors investigated the effect of CYP2C19 genotype on exposure and therapeutic failure of escitalopram in a large patient population. METHOD: A total of 4,228 escitalopram serum concentration measurements from 2,087 CYP2C19-genotyped patients 10-30 hours after drug intake were collected retrospectively from the drug monitoring database at Diakonhjemmet Hospital in Oslo...
January 12, 2018: American Journal of Psychiatry
https://www.readbyqxmd.com/read/29322841/the-effect-of-lycopene-on-cytochrome-p450-isoenzymes-and-p-glycoprotein-by-using-human-liver-microsomes-and-caco-2-cell-monolayer-model
#13
Lingti Kong, Chunli Song, Linhu Ye, Jian Xu, Daohua Guo, Qingping Shi
Lycopene is widely used as a dietary supplement. However, the effects of lycopene on cytochrome P450 (CYP) enzymes or P-glycoprotein (P-gp) are not comprehensive. The present study was performed to investigate the effects of lycopene on the CYP enzymes and P-gp activity. A cocktail method was used to evaluate the activities of CYP3A4, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. Caco-2 cell monolayer model was carried out to assay lycopene on P-gp activity. The results indicated that lycopene had a moderate inhibitory effect on CYP2E1, with IC50 value of 43...
January 11, 2018: International Journal of Food Sciences and Nutrition
https://www.readbyqxmd.com/read/29320899/in-vitro-analysis-of-itraconazole-cis-diastereoisomers-inhibition-of-nine-cytochrome-p450-enzymes-stereoselective-inhibition-of-cyp3a
#14
Kristyna Krasulova, Zdenek Dvorak, Pavel Anzenbacher
Itraconazole (ITZ), an antifungal azole derivate is a chiral drug that consists of four cis-diastereoisomers ((+)-2R,4S,2'R-ITZ-A; (+)-2R,4S,2'S-ITZ-B; (-)2S,4R,2'S-ITZ-C and (-) 2S,4R,2'R-ITZ-D) which may differ in their pharmacokinetics and pharmacodynamics. As itraconazole is known as a CYP3A4 inhibitor causing severe drug-drug interaction, the inhibitory potencies of its individual optical isomers towards nine drug-metabolising cytochrome P450 (including CYP3A, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1), were investigated...
January 10, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29315506/optimization-of-voriconazole-therapy-for-the-treatment-of-invasive-fungal-infections-in-adults
#15
Naveen Mangal, Issam Hamadeh, Meghan J Arwood, Larisa H Cavallari, Tanay S Samant, Kenneth P Klinker, Jurgen Bulitta, Stephan Schmidt
Therapeutic concentrations of voriconazole in invasive fungal infections (IFIs) are ensured using drug monitoring approach, which relies on attainment of steady state pharmacokinetics. For voriconazole, time to reach steady state can vary from 5-7 days, not optimal for critically ill patients. We developed a population pharmacokinetic/pharmacodynamic model-based approach to predict doses which can maximize the net benefit (probability of efficacy - probability of adverse events) and ensure therapeutic concentrations, early on during treatment...
January 9, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29314710/different-in-vitro-and-in-vivo-tools-for-elucidating-the-human-metabolism-of-alpha-cathinone-derived-drugs-of-abuse
#16
Sascha K Manier, Lilian H J Richter, Jan Schäper, Hans H Maurer, Markus R Meyer
In vitro and in vivo experiments are widely used for studying the metabolism of new psychoactive substances (NPS). The availability of such data is required for toxicological risk assessments and development of urine screening approaches. This study investigated the in vitro metabolism of the five pyrrolidinophenone-derived NPS alpha-pyrrolidinobutyrophenone (alpha-PBP), alpha-pyrrolidinopentiothiophenone (alpha-PVT), alpha-pyrrolidinohexanophenone (alpha-PHP), alpha-pyrrolidinoenanthophenone (alpha-PEP, PV8), and alpha-pyrrolidinooctanophenone (alpha-POP, PV9)...
January 4, 2018: Drug Testing and Analysis
https://www.readbyqxmd.com/read/29313967/clinical-pharmacogenetics-implementation-consortium-cpic-guidelines-for-cyp2c19-and-voriconazole-therapy
#17
(no author information available yet)
No abstract text is available yet for this article.
February 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29311135/clinical-pharmacokinetics-and-the-impact-of-genetic-polymorphism-on-a-cyp2c19-substrate-bms-823778-in-healthy-subjects
#18
Jiachang Gong, Lars Hansen, Lisa Iacono
BMS-823778 is a potent and selective inhibitor of 11beta-HSD1, an enzyme that regulates tissue specific intracellular glucocorticoid metabolism and a compelling target for the treatment of metabolic diseases. Metabolism of BMS-823778 was mainly mediated by polymorphic CYP2C19 with minor contribution from CYP3A3/5 and UGT1A4. Clinical PK of BMS-823778 was first investigated in healthy volunteers after single and multiple ascending doses. BMS-823778 was rapidly absorbed after oral dose, and systemic exposure at steady state increased proportionally to the dose...
January 8, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29301387/pharmacogenetics-of-vascular-risk-factors-in-alzheimer-s-disease
#19
REVIEW
Ramón Cacabelos, Arun Meyyazhagan, Juan C Carril, Pablo Cacabelos, Óscar Teijido
Alzheimer's disease (AD) is a polygenic/complex disorder in which genomic, epigenomic, cerebrovascular, metabolic, and environmental factors converge to define a progressive neurodegenerative phenotype. Pharmacogenetics is a major determinant of therapeutic outcome in AD. Different categories of genes are potentially involved in the pharmacogenetic network responsible for drug efficacy and safety, including pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes. However, most drugs exert pleiotropic effects that are promiscuously regulated for different gene products...
January 3, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29297772/assessment-of-drug-drug-interaction-potential-and-pbpk-modeling-of-cc-223-a-potent-inhibitor-of-the-mammalian-target-of-rapamycin-kinase
#20
Zeen Tong, Rangaraj Narayanan, Christian Atsriku, Jim Nissel, Yan Li, Hong Liu, Xiaomin Wang, Sekhar Surapaneni
1. CC-223 was studied in vitro for metabolism and drug-drug interactions (DDI), and in clinic for interaction with ketoconazole. 2. In vitro, human metabolites of CC-223 included O-desmethyl CC-223 (M1), keto (M2), N-oxide (M3), and imine (M13), with M1 being the most prominent metabolite. 3. CC-223 was metabolized by CYP2C9 and CYP3A, while metabolism of M1 was mediated by CYP2C8 and CYP3A. Ketoconazole increased CC-223 and M1 exposure by 60-70% in healthy volunteers. 4. CC-223 (IC50 ≥ 27 µM) and M1 (IC50 ≥ 46 µM) were inhibitors of CYP2C9 and CYP2C19 in human liver microsomes...
January 3, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
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