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https://www.readbyqxmd.com/read/28649054/effect-of-vkorc1-and-cyp2c9-polymorphisms-on-warfarin-dose-requirement-in-bangladeshi-population
#1
Zahid Sadek Chowdhury, Farah Shahjin, Farhana Akter, Maizbhauddin Ahmed, Mohammad Safiqul Islam, Muhammad Shahdaat Bin Sayeed, Reazul Islam, Abul Hasnat
Warfarin, an oral anticoagulant is one of the most widely prescribed drugs in modern medicine. Large inter-individuals variability due to age, gender, diet, concurrent drug interactions and variations in CYP2C9 and VKORC1 genes make the management of warfarin therapy challenging and yet no study has been conducted on the Bangladeshi population. The aim of the study was to identify the role of VKORC1 and CYP2C9 polymorphisms in Bangladeshi population in dose requirement of warfarin. We studied 87 heart valve replacement patients who were prescribed warfarin for minimum of 6 months with a target International normalized ratio of 2...
March 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28639488/prenatal-exposure-to-serotonin-reuptake-inhibitors-and-congenital-heart-anomalies-an-exploratory-pharmacogenetics-study
#2
Aizati N A Daud, Jorieke E H Bergman, Wilhelmina S Kerstjens-Frederikse, Pieter van der Vlies, Eelko Hak, Rolf M F Berger, Henk Groen, Bob Wilffert
AIM: To explore the role of pharmacogenetics in determining the risk of congenital heart anomalies (CHA) with prenatal use of serotonin reuptake inhibitors. METHODS: We included 33 case-mother dyads and 2 mother-only (child deceased) cases of CHA in a case-only study. Ten genes important in determining fetal exposure to serotonin reuptake inhibitors were examined: CYP1A2, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC6A4, HTR1A, HTR1B, HTR2A and HTR3B. RESULTS: Among the exposed cases, polymorphisms that tended to be associated with an increased risk of CHA were SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 and rs6298 and HTR3B rs1176744, but none reached statistical significance due to our limited sample sizes...
June 22, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28639119/a-pharmacokinetic-drug-drug-interaction-study-between-selexipag-and-midazolam-a-cyp3a4-substrate-in-healthy-male-subjects
#3
Pierre-Eric Juif, Margaux Boehler, Yves Donazzolo, Shirin Bruderer, Jasper Dingemanse
PURPOSE: In vitro data showed that selexipag and its active metabolite (ACT-333679) have an inductive effect on CYP3A4, CYP2B6, and CYP2C9 at concentrations approximately 100-fold higher than the maximum plasma concentration (C max) measured under steady-state conditions. In order to confirm in vivo the lack of induction at the enterocyte level, we assessed the effect of selexipag on midazolam, a substrate of hepatic and intestinal CYP3A4. METHODS: This study was conducted according to an open-label, randomized, two-way crossover design...
June 21, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28638342/warfarin-anticoagulation-therapy-in-caribbean-hispanics-of-puerto-rico-a-candidate-gene-association-study
#4
Karla Claudio-Campos, Aurora Labastida, Alga Ramos, Andrea Gaedigk, Jessicca Renta-Torres, Dariana Padilla, Giselle Rivera-Miranda, Stuart A Scott, Gualberto Ruaño, Carmen L Cadilla, Jorge Duconge-Soler
Existing algorithms account for ~50% of observed variance in warfarin dose requirements after including common polymorphisms. However, they do not perform as well in populations other than Caucasians, in part because some ethno-specific genetic variants are overlooked. The objective of the present study was to identify genetic polymorphisms that can explain variability in warfarin dose requirements among Caribbean Hispanics of Puerto Rico. Next-Generation Sequencing of candidate genes CYP2C9 and VKORC1 and genotyping by DMET® Plus Assay of cardiovascular patients were performed...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28626479/the-allele-frequency-of-cyp2c9-and-vkorc1-in-the-southern-khorasan-population
#5
Fariba Emadian Razavi, Asghar Zarban, Fatemeh Hajipoor, Mohsen Naseri
The genetic factors are determinants in required dosage changes of warfarin among which are polymorphisms of CYP2C9 and VKORC1 genes. The present study aimed to determine the allele and genotype frequency of CYP2C9 and VKORC1 genes in Birjand population. This study was conducted on 120 individuals who referred to Imam Reza and Vali-Asr hospitals for PT/INR test. After extracting the genomic DNA, the considered sequences were amplified by PCR, and restriction fragment length polymorphism analysis was done by AvaII and KpnI enzymes to determine allele polymorphisms...
June 2017: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28620303/effect-of-genetic-variability-in-the-cyp4f2-cyp4f11-and-cyp4f12-genes-on-liver-mrna-levels-and-warfarin-response
#6
J E Zhang, Kathrin Klein, Andrea L Jorgensen, Ben Francis, Ana Alfirevic, Stephane Bourgeois, Panagiotis Deloukas, Ulrich M Zanger, Munir Pirmohamed
Genetic polymorphisms in the gene encoding cytochrome P450 (CYP) 4F2, a vitamin K oxidase, affect stable warfarin dose requirements and time to therapeutic INR. CYP4F2 is part of the CYP4F gene cluster, which is highly polymorphic and exhibits a high degree of linkage disequilibrium, making it difficult to define causal variants. Our objective was to examine the effect of genetic variability in the CYP4F gene cluster on expression of the individual CYP4F genes and warfarin response. mRNA levels of the CYP4F gene cluster were quantified in human liver samples (n = 149) obtained from a well-characterized liver bank and fine mapping of the CYP4F gene cluster encompassing CYP4F2, CYP4F11, and CYP4F12 was performed...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28609430/polymorphisms-in-cyp2c9-are-associated-with-response-to-indomethacin-among-neonates-with-patent-ductus-arteriosus
#7
Caitlin J Smith, Kelli K Ryckman, Timothy M Bahr, John M Dagle
BACKGROUND: PDA is a common complication seen in preterm infants. Indomethacin is routinely used to treat PDA. Evidence suggests that indomethacin response is highly heritable. This study investigated the association between SNPs in CYP2C9 and PDA closure in response to indomethacin. METHODS: Six SNPs in CYP2C9 were analyzed for association with indomethacin response. A case-control analysis was performed among neonates who responded to indomethacin (responders) and neonates who required surgical ligation (non-responders)...
June 13, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28608988/should-the-dosing-algorithms-for-vitamin-k-antagonists-be-centered-around-only-vkorc1-and-cyp2c9-genotypes
#8
Tejasvita Gaikwad, Kanjaksha Ghosh, Shrimati Shetty
We read with interest the recent report by Baranova et al. [1] in which authors have carried out secondary analysis of European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) data by evaluating the performance of different dosing algorithms and time intervals of outcome assessment across VKORC1- CYP2C9 genetic sub groups. This article is protected by copyright. All rights reserved.
June 13, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28604475/analysis-of-the-variables-influencing-valproic-acid-concentration-in-the-serum-and-cerebrospinal-fluid-of-chinese-patients-after-craniotomy
#9
Li Zhi-Hong, Gao Wei-Qi, Liu Gui-Fen, Chen Wei-Hong
BACKGROUND: Valproic acid (VPA) has been widely used in Chinese patients after craniotomy. Many studies have focused on the influencing factors of VPA serum concentration, but conclusions are sometimes paradoxical. Furthermore, the concentration of VPA in the cerebrospinal fluid (CSF) has been rarely reported. In the present study, VPA CSF concentrations were measured and the potential factors influencing serum concentration and CSF distribution of VPA were investigated. In addition, the functional relationship between serum and CSF concentration was explored...
June 8, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28603631/hepatic-expression-profiles-in-retroviral-infection-relevance-to-drug-hypersensitivity-risk
#10
Yat Yee Wong, Brian Johnson, Thomas C Friedrich, Lauren A Trepanier
HIV-infected patients show a markedly increased risk of delayed hypersensitivity (HS) reactions to potentiated sulfonamide antibiotics (trimethoprim/sulfamethoxazole or TMP/SMX). Some studies have suggested altered SMX biotransformation in HIV infection, but hepatic biotransformation pathways have not been evaluated directly. Systemic lupus erythematosus (SLE) is another chronic inflammatory disease with a higher incidence of sulfonamide HS, but it is unclear whether retroviral infection and SLE share risk factors for drug HS...
June 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28579309/genetic-variation-in-the-first-pass-metabolism-of-ethinylestradiol-sex-hormone-binding-globulin-levels-and-venous-thrombosis-risk
#11
Bernardine H Stegeman, Hans L Vos, Frans M Helmerhorst, Frits R Rosendaal, Pieter H Reitsma, Astrid van Hylckama Vlieg
BACKGROUND: Use of ethinylestradiol, one of the active ingredients in combined oral contraceptives, affects the incidence of venous thrombosis. To explain why some women develop thrombosis when using oral contraceptives and others do not, we hypothesized a role for the first-pass metabolism of ethinylestradiol in the liver. We set out to determine the association between genetic variation in the first-pass metabolism of ethinylestradiol, venous thrombosis risk and the effect on Sex-hormone-binding-globulin (SHBG) levels...
July 2017: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/28550460/the-impact-of-non-genetic-and-genetic-factors-on-a-stable-warfarin-dose-in-thai-patients
#12
Nitsupa Wattanachai, Sutthida Kaewmoongkun, Burabha Pussadhamma, Pattarapong Makarawate, Chaiyasith Wongvipaporn, Songsak Kiatchoosakun, Suda Vannaprasaht, Wichittra Tassaneeyakul
PURPOSE: The aim of this study was to investigate the contributions of non-genetic and genetic factors on the variability of stable warfarin doses in Thai patients. METHODS: A total of 250 Thai patients with stable warfarin doses were enrolled in the study. Demographics and clinical data, e.g., age, body mass index, indications for warfarin and concomitant medications, were documented. Four single nucleotide polymorphisms in the VKORC1 - 1639G > A, CYP2C9*3, CYP4F2 rs2108622, and UGT1A1 rs887829 genes were detected from gDNA using TaqMan allelic discrimination assays...
May 26, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28546997/pharmacogenomic-findings-from-clinical-whole-exome-sequencing-of-diagnostic-odyssey-patients
#13
Margot A Cousin, Eric T Matey, Patrick R Blackburn, Nicole J Boczek, Tammy M McAllister, Teresa M Kruisselbrink, Dusica Babovic-Vuksanovic, Konstantinos N Lazaridis, Eric W Klee
BACKGROUND: We characterized the pharmacogenomics (PGx) results received by diagnostic odyssey patients as secondary findings during clinical whole exome sequencing (WES) testing as a part of their care in Mayo Clinic's Individualized Medicine Clinic to determine the potential benefits and limitations to this cohort. METHODS: WES results on 94 patients included a subset of PGx variants in CYP2C19,CYP2C9, and VKORC1 if identified in the patient. Demographic, phenotypic, and medication usage information was abstracted from patient medical data...
May 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28534260/pharmacogenetics-of-cannabinoids
#14
Szymon Hryhorowicz, Michal Walczak, Oliwia Zakerska-Banaszak, Ryszard Słomski, Marzena Skrzypczak-Zielińska
Although the application of medical marijuana and cannabinoid drugs is controversial, it is a part of modern-day medicine. The list of diseases in which cannabinoids are promoted as a treatment is constantly expanding. Cases of significant improvement in patients with a very poor prognosis of glioma or epilepsy have already been described. However, the occurrence of side effects is still difficult to estimate, and the current knowledge of the therapeutic effects of cannabinoids is still insufficient. In our opinion, the answers to many questions and concerns regarding the medical use of cannabis can be provided by pharmacogenetics...
May 22, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28522373/population-pharmacokinetics-of-carvedilol-enantiomers-and-their-metabolites-in-healthy-subjects-and-type-2-diabetes-patients
#15
Glauco H B Nardotto, Vera L Lanchote, Eduardo B Coelho, Oscar Della Pasqua
Carvedilol, a drug available as a racemic mixture, is metabolised into hydroxyphenylcarvedilol (OHC) by CYP2D6 and O-desmethylcarvedilol (DMC) by CYP2C9 followed by conjugation to glucuronides. In contrast to other β-adrenergic receptor antagonists, carvedilol does not induce insulin resistance or worsen glycaemic control in diabetic hypertensive patients. This study aims to investigate the implications of type 2 diabetes (T2DM) on the pharmacokinetics of carvedilol enantiomers using an integrated population pharmacokinetic modelling approach...
May 15, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28522025/corrigendum-to-genetic-polymorphism-of-cynomolgus-and-rhesus-macaque-cyp2c9-drug-metab-pharmacokinet-30-2015-130-132
#16
Yasuhiro Uno, Akinori Matsushita, Norie Murayama, Hiroshi Yamazaki
No abstract text is available yet for this article.
June 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28515818/pharmacogenomic-testing-for-psychotropic-medication-selection-a-systematic-review-of-the-assurex-genesight-psychotropic-test
#17
(no author information available yet)
BACKGROUND: A large proportion of the Ontario population lives with a diagnosed mental illness. Nearly 5% of Ontarians have major depressive disorder, and another 5% have another type of depressive disorder, bipolar disorder, schizophrenia, anxiety, or some other disorder not otherwise specified. Medications are commonly used to treat mental illness, but choosing the right medication for each patient is challenging, and more than 40% of patients discontinue their medication within 90 days because of adverse effects or lack of response...
2017: Ontario Health Technology Assessment Series
https://www.readbyqxmd.com/read/28513222/the-contribution-of-cyp2c-gene-subfamily-involved-in-epoxygenase-pathway-of-arachidonic-acids-metabolism-to-hypertension-susceptibility-in-russian-population
#18
Alexey Polonikov, Marina Bykanova, Irina Ponomarenko, Svetlana Sirotina, Anna Bocharova, Kseniya Vagaytseva, Vadim Stepanov, Mikhail Churnosov, Olga Bushueva, Maria Solodilova, Yaroslav Shvetsov, Vladimir Ivanov
Numerous studies demonstrated an importance of cytochrome P-450 epoxygenase pathway of arachidonic acids metabolism for the pathogenesis of essential hypertension (EH). The present study was designed to investigate whether common single-nucleotide polymorphisms (SNP) of CYP2C gene subfamily such as CYP2C8 (rs7909236 and rs1934953), CYP2C9 (rs9332242), and CYP2C19 (rs4244285) are associated with susceptibility to EH in Russian population. A total of 816 unrelated Russian individuals comprising 425 EH patients and 391 normotensive controls were included into the study...
2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28506184/complications-of-psychotropic-and-pain-medications-in-an-ultrarapid-metabolizer-patient-at-the-upper-1-of-cytochrome-p450-cyp450-function-quantified-by-combinatorial-cyp450-genotyping
#19
Gualberto Ruaño, Karen Larsen, Mohan Kocherla, James Samuel Graydon, Jonathan Kost
A 44-year-old Caucasian woman presented with a history of empirical treatment with 20 pain and psychotropic medications, as well as dual comorbidity of intractable pain and depression. A multiple gain-of-function profile in the CYP450 family of cytochrome P450 (CYP450) drug metabolism isoenzymes was discovered. The patient was a homozygote of suprafunctional alleles for both CYP2D6 ((*)35/(*)35) and CYP2C19 ((*)17/(*)17) genes and functional alleles for CYP2C9 ((*)1/(*)1), which account for aggregate drug metabolism function at the upper 1% of the population...
June 2017: Journal of Pain & Palliative Care Pharmacotherapy
https://www.readbyqxmd.com/read/28502675/genotype-guided-dosing-of-warfarin-through-modeling-and-simulation
#20
Jiexin Deng, Valvanera Vozmediano Esteban, Monica Rodriguez, Larisa H Cavallari, Stephan Schmidt
Current genotype-guided algorithms for warfarin dosing fail to deliver optimal performance in two aspects: 1) these algorithms are not able to achieve the same level of benefits in non-white populations, since they were developed based on multivariate regression analysis with mostly European/White data and did not include genetic variants found frequently in non-white populations; 2) these algorithms do not account for the dynamic dose/response relationship and were limited in their usefulness to guide dosing during the initiation phase, as the possession of variant VKORC1 and/or CYP2C9 polymorphisms has been associated with a more rapid attainment of target international normalized ratio (INR) and higher risk of over-anticoagulation even in genotype-guided patients...
May 11, 2017: European Journal of Pharmaceutical Sciences
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