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https://www.readbyqxmd.com/read/29241501/cyp2d6-drug-gene-and-drug-drug-gene-interactions-among-patients-prescribed-pharmacogenetically-actionable-opioids
#1
Mitchell R Knisely, Janet S Carpenter, Claire Burke Draucker, Todd Skaar, Marion E Broome, Ann M Holmes, Diane Von Ah
PURPOSE: When codeine and tramadol are used for pain management, it is imperative that nurses are able to assess for potential drug-gene and drug-drug-gene interactions that could adversely impact drug metabolism and ultimately pain relief. Both drugs are metabolized through the CYP2D6 metabolic pathway which can be affected by medications as well the patient's own pharmacogenotype. The purpose of this brief report is to identify drug-gene and drug-drug-gene interactions in 30 adult patients prescribed codeine or tramadol for pain...
December 2017: Applied Nursing Research: ANR
https://www.readbyqxmd.com/read/29233455/genetic-variation-of-cytochrome-p450-in-uyghur-chinese-population
#2
Guangzhao Qi, Duolu Li, Xiaojian Zhang
Interindividual and interethnic variability of drug responses could be attributed to the differences of genetic polymorphisms in the drug metabolizing enzymes and transporters genes among the populations. Here we reviewed the studies of genetic variations in Uyghur Chinese of fifteen CYP450 genes including CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP2J2, CYP2W1, CYP3A4, CYP3A5, CYP4A11, and CYP17A1, which totally covered 277 variants. We also collected the data of 277 variants covered in our study in two extensive population sequencing projects, the International HapMap Project (Hap-Map) and the 1000 Genomes Project and compared them with the data of Uyghur Chinese...
March 6, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29205295/protein-abundance-of-clinically-relevant-drug-metabolizing-enzymes-in-the-human-liver-and-intestine-a-comparative-analysis-in-paired-tissue-specimens
#3
M Drozdzik, D Busch, J Lapczuk, J Müller, M Ostrowski, M Kurzawski, S Oswald
The work revises and complements existing findings on the distribution of drug metabolizing enzymes' in the first-pass effect organs. We explored gene expression (qPCR) and protein abundance (LC-MS/MS) of CYP1A2, CYP2B6, CYP2C8/9/19, CYP2D6, CYP2E1, CYP3A4/5, UGT1A1/3, UGT2B7/15 in the liver, duodenum, jejunum, ileum and colon in paired tissues from 9 organ donors. All proteins were detected in the liver, but in the intestine CYP2C9/19, CYP2D6, CYP3A4/5, UGT1A1/3 and UGT2B7 were found. CYP3A4 showed comparable abundance in the liver and jejunum, whereas other enzymes were markedly higher in the hepatic tissue...
December 5, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29196917/development-of-a-linear-dual-column-hplc-ms-ms-method-and-clinical-genetic-evaluation-for-tramadol-and-its-phase-i-and-ii-metabolites-in-oral-fluid
#4
Hyerim Yu, Seongkuk Hong, Chul-Ho Jeong, Jung-Woo Bae, Sooyeun Lee
Tramadol is a centrally acting synthetic opioid analgesic and has received special attention due to its abuse potential and unexpected responses induced by CYP2D6 polymorphism. Oral fluid is an advantageous biofluid for drug analysis due to non-invasive sampling and high correlation of drug concentrations with plasma. However, few studies have been performed on distribution of tramadol and its metabolites in oral fluid. In the present study, a linear dual column HPLC-MS/MS method was developed and fully validated for the simultaneous determination of tramadol and its phase I [O-desmethyltramadol (ODMT), N-desmethyltramadol (NDMT) and N,O-didesmethyltramadol (NODMT)] and II metabolites in oral fluid...
December 1, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29193123/physiologically-based-pharmacokinetic-modeling-to-evaluate-the-systemic-exposure-of-gefitinib-in-cyp2d6-ultrarapid-metabolizers-and-extensive-metabolizers
#5
Yingxue Chen, Diansong Zhou, Weifeng Tang, Wangda Zhou, Nidal Al-Huniti, Eric Masson
Gefitinib is a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase and is used for the treatment of non-small-cell lung cancer (NSCLC) with activating EGFR mutations. Gefitinib is metabolized by CYP2D6 and CYP3A4. This analysis compared the systemic exposure of gefitinib after oral administration in CYP2D6 ultrarapid metabolizers (UM) vs extensive metabolizers (EM). Physiologically based pharmacokinetic (PBPK) modeling was conducted using a population-based simulator. The model was calibrated using itraconazole-gefitinib clinical drug-drug interaction data and validated with gefitinib data in CYP2D6 EM vs poor metabolizers (PM)...
November 28, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29190510/predicted-activity-of-ugt2b7-abcb1-oprm1-and-comt-using-full-gene-haplotypes-and-their-association-with-the-cyp2d6-inferred-metabolizer-phenotype
#6
Frank R Wendt, Antti Sajantila, Bruce Budowle
The pharmacogene, CYP2D6, is commonly used to infer metabolizer phenotype of many marketed drugs and endogenous toxins in ante- and post-mortem patients but only represents the efficiency of phase 1 metabolism. Downstream metabolic enzymes encoded by UGT2B7, ABCB1, OPRM1, and COMT also have been implicated in variable individual response to drugs due to their activity at different stages of the tramadol ADME (absorption, distribution, metabolism, and excretion) process. While commonly studied as single genes using targeted genotyping approaches, a more comprehensive tramadol metabolism profile has not been evaluated...
November 26, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/29183390/serum-concentrations-of-active-tamoxifen-metabolites-predict-long-term-survival-in-adjuvantly-treated-breast-cancer-patients
#7
Thomas Helland, Nina Henne, Ersilia Bifulco, Bjørn Naume, Elin Borgen, Vessela N Kristensen, Jan T Kvaløy, Timothy L Lash, Grethe I G Alnæs, Ron H van Schaik, Emiel A M Janssen, Steinar Hustad, Ernst A Lien, Gunnar Mellgren, Håvard Søiland
BACKGROUND: Controversies exist as to whether the genetic polymorphisms of the enzymes responsible for the metabolism of tamoxifen can predict breast cancer outcome in patients using adjuvant tamoxifen. Direct measurement of concentrations of active tamoxifen metabolites in serum may be a more biological plausible and robust approach. We have investigated the association between CYP2D6 genotypes, serum concentrations of active tamoxifen metabolites, and long-term outcome in tamoxifen treated breast cancer patients...
November 28, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29182577/estrogen-metabolism-associated-cyp2d6-and-il6-174g-c-polymorphisms-in-schistosoma-haematobium-infection
#8
Rita Cardoso, Pedro C Lacerda, Paulo P Costa, Ana Machado, André Carvalho, Adriano Bordalo, Ruben Fernandes, Raquel Soares, Joachim Richter, Helena Alves, Monica C Botelho
Schistosoma haematobium is a human blood fluke causing a chronic infection called urogenital schistosomiasis. Squamous cell carcinoma of the urinary bladder (SCC) constitutes chronic sequelae of this infection, and S. haematobium infection is accounted as a risk factor for this type of cancer. This infection is considered a neglected tropical disease and is endemic in numerous countries in Africa and the Middle East. Schistosome eggs produce catechol-estrogens. These estrogenic molecules are metabolized to active quinones that induce modifications in DNA...
November 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29181698/pharmacokinetics-of-cyp2c9-cyp2c19-and-cyp2d6-substrates-in-healthy-chinese-and-european-subjects
#9
Sijie Lu, R A Nand, J S Yang, Gang Chen, A S Gross
PURPOSE: The aim of this analysis is to compare the pharmacokinetics of drug substrates in healthy Chinese and European subjects of aligned CYP2C9, CYP2C19, or CYP2D6 enzyme activity, providing further insight into drivers of interethnic differences in pharmacokinetics. METHODS: Following identification of appropriate drug substrates, a comprehensive and structured literature search was conducted to identify single-dose pharmacokinetic data in healthy Chinese or European subjects with reported CYP2C9, CYP2C19, or CYP2D6 activity (genotype or phenotype)...
November 27, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29180876/the-effect-of-cyp2d6-10-polymorphism-on-adjuvant-tamoxifen-in-asian-breast-cancer-patients-a-meta-analysis
#10
Junjun Lu, He Li, Peng Guo, Rui Shen, Yingbin Luo, Qiao Ge, Wenfei Shi, Yan Li, Weikang Zhu
Objective: To evaluate the effect of CYP2D6 *10 polymorphism (C 100C>T, rs1065852) on clinical outcomes of female Asian breast cancer patients with tamoxifen adjuvant treatment. Methods: Meta-analysis of retrospective cohort studies published in July 2017 was performed. Fifteen studies with 1,794 Asian breast cancer patients were included, using strict eligibility requirements. Associations of disease-free survival (DFS), overall survival (OS) and recurrence rate after tamoxifen intake, with CYP2D6 *10 polymorphism were investigated through random effects models...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29168799/modulation-of-cytochrome-p450-p-glycoprotein-and-pregnane-x-receptor-by-selected-antimalarial-herbs-implication-for-herb-drug-interaction
#11
Pius S Fasinu, Vamshi K Manda, Olivia R Dale, Nosa O Egiebor, Larry A Walker, Shabana I Khan
Seven medicinal plants popularly used for treating malaria in West Africa were selected to assess herb-drug interaction potential through a series of in vitro methods. Fluorescent cytochrome P450 (CYP) assays were conducted using the recombinant CYP enzymes for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 to assess the effect of the methanolic extracts on the metabolic activity of CYPs. Secondly, the inhibitory effect of the extracts was evaluated on P-glycoproteins (P-gp) using calcein-AM, a fluorescent substrate, in MDCK-II and hMDR1-MDCK-II cells...
November 23, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29166542/identification-of-cytochrome-p450-cyp-isoforms-involved-in-the-metabolism-of-artocarpin-and-assessment-of-its-drug-drug-interaction-ddi
#12
Wei Qu, Xuezheng Liu
Artocarpin isolated from an agricultural plant Artocarpus communis has shows anti-inflammation and anticancer activities. In this study, we utilized recombinant human UDP-glucuronosyltransferasesupersomes (UGTs) and human liver microsomes (HLMs) to explore its inhibitory effect on UGTs and cytochrome p450 enzymes(CYPs). Chemical inhibition studies and screening assays with recombinant human CYPs were used to identify if CYP isoform is involved in artocarpin metabolism. Artocarpin showed strong inhibition against UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B7, CYP2C8 and CYP3A4...
November 22, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29164956/have-we-successfully-implemented-cyp2d6-genotyping-in-psychiatry
#13
Jose de Leon
No abstract text is available yet for this article.
November 22, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29153926/pharmacokinetics-of-risperidone-in-different-application-forms-comparing-long-acting-injectable-and-oral-formulations
#14
Georgios Schoretsanitis, Jose de Leon, Ekkehard Haen, Benedikt Stegmann, Christoph Hiemke, Gerhard Gründer, Michael Paulzen
We aimed to explore the differences in the pharmacokinetics of risperidone between oral and long-acting injectable (LAI) formulations using a large database of therapeutic drug monitoring (TDM). Plasma concentrations of risperidone (RIS), its active metabolite (9-OH-RIS) and the active moiety (AM) (RIS+9-OH-RIS), their concentration-to-dose (C/D) ratios and ratio of RIS/9-OH-RIS (an index of CYP2D6 metabolic activity) were used to compare patients receiving risperidone orally (n = 851) and those treated with LAI RIS (n = 63)...
November 16, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29150839/liver-injury-induced-by-clomiphene-citrate-a-case-report-and-literature-reviews
#15
H-M Zhang, X-H Zhao, Y-F He, L-R Sun
WHAT IS KNOWN AND OBJECTIVE: Clomiphene citrate is used to cause ovulation in females and to increase semen production in males. Clomiphene citrate is well tolerated in most patients and rarely induces liver injury. We report a case of liver injury which is associated with administration of clomiphene citrate in a male patient. CASE SUMMARY: A 31-year-old man who was treated by clomiphene citrate for 5 days was transferred to our emergency room with reddish-brown urine and upper abdominal pain...
November 17, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29137842/comparison-of-pharmacokinetics-of-newly-discovered-aromatase-inhibitors-by-a-cassette-microdosing-approach-in-healthy-japanese-subjects
#16
Hiroyuki Kusuhara, Tadayuki Takashima, Hisako Fujii, Tsutomu Takashima, Masaaki Tanaka, Akira Ishii, Shusaku Tazawa, Kazuhiro Takahashi, Kayo Takahashi, Hidekichi Tokai, Tsuneo Yano, Makoto Kataoka, Akihiro Inano, Suguru Yoshida, Takamitsu Hosoya, Yuichi Sugiyama, Shinji Yamashita, Taisuke Hojo, Yasuyoshi Watanabe
The aim of the present study is to investigate the pharmacokinetics of our newly developed aromatase inhibitors (cetrozole and TMD-322) in healthy subjects by a cassette microdose strategy. A cocktail of cetrozole and TMD-322 was administered intravenously or orally (1.98 μg for each drug) to six healthy volunteers in a crossover fashion. Anastrozole (1.98 μg) was also included in the oral cocktail. Total body clearance and bioavailability were 12.1 ± 7.1 mL/min/kg and 34.9 ± 32.3% for cetrozole, and 16...
September 21, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29137046/multiple-adverse-drug-reactions-and-genetic-polymorphism-testing-a-case-report-with-negative-result
#17
Ana Lucía Arellano, Marta Martin-Subero, Mar Monerris, Adrián LLerena, Magí Farré, Eva Montané
RATIONALE: Defects in drug metabolic pathways could explain why some patients have a history of multiple adverse drug reactions (ADR); therefore we aimed to analyze genetic polymorphisms in a patient with multiple ADR related to drugs with a common hepatic metabolic pathway through CYP2D6. PATIENT CONCERNS: We report a patient with psychosis and hypertension related to amitriptyline, tramadol, and duloxetine within a 2-year period. INTERVENTIONS AND OUTCOMES: A pharmacogenetic test was performed to assess the causative role of the CYP2D6 enzyme, but did not demonstrate a metabolic deficiency...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29136336/effect-of-polymorphisms-on-the-pharmacokinetics-pharmacodynamics-and-safety-of-sertraline-in-healthy-volunteers
#18
Miriam Saiz-Rodríguez, Carmen Belmonte, Manuel Román, Dolores Ochoa, Dora Koller, María Talegón, María C Ovejero-Benito, Rosario López-Rodríguez, Teresa Cabaleiro, Francisco Abad-Santos
Sertraline is a selective serotonin reuptake inhibitor (SSRI) widely metabolized in the liver by cytochrome P450 (CYP) enzymes. Besides, it is a P-glycoprotein substrate. Moreover, serotonin transporters and serotonin receptors are involved in its efficacy and safety. The aim of the present study was to evaluate the role of polymorphisms of metabolizing enzymes, transporters and receptors on the pharmacokinetics, pharmacodynamics and tolerability of sertraline in healthy volunteers. Forty-six healthy volunteers (24 men and 22 women) receiving a 100-mg single oral dose of sertraline were genotyped for 17 genetic variants of CYP enzymes (CYP2B6, CYP2C9, CYP2C19, CYP2D6), ATP binding cassette subfamily B member 1 (ABCB1), Solute carrier family 6 member 4 (SLC6A4), 5-Hydroxytryptamine receptor 2A (HTR2A) and 5-Hydroxytryptamine receptor 2C (HTR2C) genes...
November 14, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29135105/impact-of-abcb1-and-cyp2d6-polymorphisms-on-tamoxifen-treatment-outcomes-and-adverse-events-in-breast-cancer-patients
#19
Sona Argalacsova, Ondrej Slanar, Hana Bakhouche, Lubos Pertuzelka
PURPOSE: This study was designed to evaluate the effect of CYP2D6 and ABCB1 polymorphisms and co-medication on the outcomes and adverse events (AEs) of tamoxifen therapy. METHODS: In total, 258 women (187 postmenopausal and 71 premenopausal) with hormone positive breast carcinoma were retrospectively evaluated. CYP2D6 polymorphisms were evaluated with AmpliChip (Roche), and polymorphisms of ATP-binding cassettes B1 (P-glycoprotein) (ABCB1) rs2032582 and rs1045642 with restriction fragment length polymorphisms polymerase chain reaction (RFLP-PCR)...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29134945/drug-drug-interaction-potential-of-the-hepatitis-b-and-hepatitis-d-virus-entry-inhibitor-myrcludex-b-assessed-in-vitro
#20
Antje Blank, Katrin Meier, Stephan Urban, Walter Emil Haefeli, Johanna Weiss
BACKGROUND: Myrcludex B is a first-in-class virus entry inhibitor for patients with chronic hepatitis B or B/D infections. In patients it will be co-administered with drugs needed for the disease or comorbidities. We aimed to define the risk of drug-drug interactions by characterizing the influence of myrcludex B on relevant drug transporting and metabolizing enzymes in vitro. METHODS: Inhibition of P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP/ABCG2), and the organic anion transporting polypeptides 1B1 and 1B3 (OATP1B1/SLCO1B1 and OATP1B3/SLCO1B3) was measured in cells over-expressing the respective transporter using fluorogenic substrates...
November 14, 2017: Antiviral Therapy
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