keyword
MENU ▼
Read by QxMD icon Read
search

Cyp2d6

keyword
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
#1
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/28808272/a-combinatorial-approach-for-the-discovery-of-cytochrome-p450-2d6-inhibitors-from-nature
#2
Johannes Hochleitner, Muhammad Akram, Martina Ueberall, Rohan A Davis, Birgit Waltenberger, Hermann Stuppner, Sonja Sturm, Florian Ueberall, Johanna M Gostner, Daniela Schuster
The human cytochrome P450 2D6 (CYP2D6) enzyme is part of phase-I metabolism and metabolizes at least 20% of all clinically relevant drugs. Therefore, it is an important target for drug-drug interaction (DDI) studies. High-throughput screening (HTS) assays are commonly used tools to examine DDI, but show certain drawbacks with regard to their applicability to natural products. We propose an in silico - in vitro workflow for the reliable identification of natural products with CYP2D6 inhibitory potential. In order to identify candidates from natural product-based databases that share similar structural features with established inhibitors, a pharmacophore model was applied...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28803404/polymorphisms-in-xrcc1-ercc2-and-ercc3-dna-repair-genes-cyp1a1-xenobiotic-metabolism-gene-and-tobacco-are-associated-with-bladder-cancer-susceptibility-in-tunisian-population
#3
Molka Feki-Tounsi, Rim Khlifi, Ibtihel Louati, Mohamed Fourati, Mohamed-Nabil Mhiri, Amel Hamza-Chaffai, Ahmed Rebai
Other than the established environmental risk factors associated with bladder cancer (BC), little is known about the genetic variations determining the individual susceptibility of this complex disease. This study aimed to investigate the relationship of BC with environmental agents and polymorphisms in XRCC1, ERCC2, and ERCC3 DNA repair genes and CYP1A1, CYP2D6, NAT1, and NAT2 xenobiotic metabolism genes through a hospital-based case-control study in Tunisia. The selection of the single nucleotide polymorphisms (SNPs) (rs25487, rs 13181, rs415407, rs446421, rs1058172, rs4921880, and rs1208) was performed using the dbSNP database...
August 12, 2017: Environmental Science and Pollution Research International
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
#4
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
#5
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/28777243/systematic-evaluation-of-commercial-pharmacogenetic-testing-in-psychiatry-a-focus-on-cyp2d6-and-cyp2c19-allele-coverage-and-results-reporting
#6
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
#7
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 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28774812/cytochrome-p450-inhibition-by-three-licorice-species-and-fourteen-licorice-constituents
#8
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/28774688/prenatal-exposure-to-drinking-water-chlorination-by-products-cytochrome-p450-gene-polymorphisms-and-small-for-gestational-age-neonates
#9
Samuella G Bonou, Patrick Levallois, Yves Giguère, Manuel Rodriguez, Alexandre Bureau
Genetic susceptibility may modulate chlorination by-products (CBPs) effects on fetal growth, especially genes coding for the cytochrome P450 involved in the metabolism of CBPs and steroidogenesis. In a case-control study of 1432 mother-child pairs, we assessed the association between maternal and child single nucleotide polymorphisms (SNPs) within CYP1A2, CYP2A6, CYP2D6 and CYP17A1 genes and small-for-gestational-age neonates (SGA<10th percentile) as well as interaction between these SNPs and maternal exposure to trihalomethanes or haloacetic acids (HAAs) during the third trimester of pregnancy...
July 31, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28769788/association-between-cyp2d6-genotypes-and-the-risk-of-antidepressant-discontinuation-dosage-modification-and-the-occurrence-of-maternal-depression-during-pregnancy
#10
Anick Bérard, Andrea Gaedigk, Odile Sheehy, Christina Chambers, Mark Roth, Pina Bozzo, Diana Johnson, Kelly Kao, Sharon Lavigne, Lori Wolfe, Dee Quinn, Kristen Dieter, Jin-Ping Zhao
Importance: Polymorphic expression of drug metabolizing enzymes affects the metabolism of antidepressants, and thus can contribute to drug response and/or adverse events. Pregnancy itself can affect CYP2D6 activity with profound variations determined by CYP2D6 genotype. Objective: To investigate the association between CYP2D6 genotype and the risk of antidepressant discontinuation, dosage modification, and the occurrence of maternal CYP2D6, Antidepressants, Depression during pregnancy. Setting: Data from the Organization of Teratology Information Specialists (OTIS) Antidepressants in Pregnancy Cohort, 2006-2010, were used...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28769582/cyp2d6-phenotypes-are-associated-with-adverse-outcomes-related-to-opioid-medications
#11
Jennifer L St Sauver, Janet E Olson, Veronique L Roger, Wayne T Nicholson, John L Black, Paul Y Takahashi, Pedro J Caraballo, Elizabeth J Bell, Debra J Jacobson, Nicholas B Larson, Suzette J Bielinski
BACKGROUND: Variation in the CYP2D6 gene may affect response to opioids in both poor and ultrarapid metabolizers, but data demonstrating such associations have been mixed, and the impact of variants on toxicity-related symptoms (e.g., nausea) is unclear. Therefore, we examined the association between CYP2D6 phenotype and poor pain control or other adverse symptoms related to the use of opioids in a sample of primary care patients. MATERIALS AND METHODS: We identified all patients in the Mayo Clinic RIGHT Protocol who were prescribed an opioid medication between July 01, 2013 and June 30, 2015, and categorized patients into three phenotypes: poor, intermediate to extensive, or ultrarapid CYP2D6 metabolizers...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28762527/outcomes-after-18-months-of-eliglustat-therapy-in-treatment-na%C3%A3-ve-adults-with-gaucher-disease-type-1-the-phase-3-engage-trial
#12
Pramod K Mistry, Elena Lukina, Hadhami Ben Turkia, Suma P Shankar, Hagit Baris, Marwan Ghosn, Atul Mehta, Seymour Packman, Gregory Pastores, Milan Petakov, Sarit Assouline, Manisha Balwani, Sumita Danda, Evgueniy Hadjiev, Andres Ortega, Sebastiaan J M Gaemers, Regina Tayag, M Judith Peterschmitt
Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive CYP2D6 metabolizers (>90% of patients). In the primary analysis of the Phase 3 ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in significant reductions in spleen and liver volumes and increases in hemoglobin concentration and platelet count compared with placebo. We report 18-month outcomes of patients who entered the trial extension period, in which all patients received eliglustat...
August 1, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28762370/impact-of-cyp2d6-polymorphisms-on-endoxifen-concentrations-and-breast-cancer-outcomes
#13
REVIEW
G S Hwang, R Bhat, R D Crutchley, M V Trivedi
We investigated the impact of germline CYP2D6 genotyping done using the non-tumor specimen on endoxifen concentrations and/or clinical outcomes in breast cancer (BC) patients treated with tamoxifen in published studies. We evaluated published data from 13 001 patients in 29 studies. Mean±s.d. endoxifen concentrations were significantly lower in poor metabolizers (PM) versus extensive metabolizers (EM) (8.8±7.2 versus 22.3±11.8 ng ml(-1); P<0.05). The PM status did not influence clinical outcomes in majority of the studies...
August 1, 2017: Pharmacogenomics Journal
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/28750151/pharmacokinetics-and-safety-of-brexpiprazole-following-multiple-dose-administration-to-japanese-patients-with-schizophrenia
#17
Jun Ishigooka, Shuichi Iwashita, Koushi Higashi, Ei Leen Liew, Yoshihiro Tadori
Brexpiprazole is currently approved in the United States for the treatment of schizophrenia and as adjunctive treatment of major depressive disorder. In Canada, it is approved for the treatment of schizophrenia. This study evaluated the pharmacokinetics (PK) and safety of brexpiprazole in Japanese patients with schizophrenia. This phase 1 study comprised a 14-day multiple-dose administration of brexpiprazole 1, 4, and 6 mg/day (n = 7, 8, and 6, respectively). Plasma concentrations and PK parameters and the influence of CYP2D6 polymorphisms (intermediate metabolizers [IMs] and extensive metabolizers [EMs]) on PK were evaluated...
July 27, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28747995/assessment-of-inhibitory-effects-on-major-human-cytochrome-p450-enzymes-by-spasmolytics-used-in-the-treatment-of-overactive-bladder-syndrome
#18
Dominik Dahlinger, Sevinc Aslan, Markus Pietsch, Sebastian Frechen, Uwe Fuhr
BACKGROUND: The objective of this study was to examine the inhibitory potential of darifenacin, fesoterodine, oxybutynin, propiverine, solifenacin, tolterodine and trospium chloride on the seven major human cytochrome P450 enzymes (CYP) by using a standardized and validated seven-in-one cytochrome P450 cocktail inhibition assay. METHODS: An in vitro cocktail of seven highly selective probe substrates was incubated with human liver microsomes and varying concentrations of the seven test compounds...
July 2017: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/28745555/the-effect-of-rs5758550-on-cyp2d6-2-phenotype-and-formation-of-endoxifen-in-breast-cancer-patients-using-tamoxifen
#19
Anabel B Sanchez-Spitman, Dirk-Jan Ar Moes, Hans Gelderblom, Vincent O Dezentjé, Jesse J Swen, Henk-Jan Guchelaar
AIM: CYP2D6*2 is considered fully active, but it has been suggested that it only happens in the presence of rs5758550. This study aims to elucidate the impact of this enhancer. MATERIALS & METHODS: DNA and blood samples from women enrolled in the CYPTAM study (NTR1509) were analyzed. Fourteen CYP2D6*2 carriers without the enhancer were reclassified. The relationship of CYP2D6 phenotypes and drug levels was studied. RESULTS: After correction for the absence of the enhancer, the correlation between CYP2D6 phenotypes and endoxifen did not improve (R(2): 0...
August 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28745549/prior-opioid-exposure-influences-parents-sharing-of-their-children-s-cyp2d6-research-results
#20
Melanie F Myers, Xue Zhang, Brooke McLaughlin, Diane Kissell, Cassandra L Perry, Matthew Veerkamp, Kejian Zhang, Ingrid A Holm, Cynthia A Prows
AIM: To determine parents' use of their children's CYP2D6 research result. We hypothesized that perceived utility, likelihood of sharing and actual sharing of results would differ between parents with children previously exposed (cases) or unexposed (controls) to opioids. METHODS: We returned results by phone (baseline). We surveyed parents about perceived utility and likelihood of sharing their child's research result at baseline, and actual sharing at 3 and 12 months...
August 2017: Pharmacogenomics
keyword
keyword
87431
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"