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Cyp2d6

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https://www.readbyqxmd.com/read/28626197/evaluation-of-cyp2d6-protein-expression-and-activity-in-the-small-intestine-to-determine-its-metabolic-capability-in-the-japanese-population
#1
Momoko Kawakami, Sachiko Takenoshita-Nakaya, Yuko Takeba, Yuki Nishimura, Masayuki Oda, Minoru Watanabe, Yuki Ohta, Shinjiro Kobayashi, Takehito Ohtsubo, Shinichi Kobayashi, Naoki Uchida, Naoki Matsumoto
CYP2D6 plays an important role in the metabolism of many drugs such as opioids and antidepressants. Polymorphisms of the CYP2D6 gene are widely observed in the Japanese population, and can affect the first-pass metabolism of orally administered drugs. Several CYP enzymes have been identified in the small intestine of Caucasians, but intestinal CYP enzymes have not been reported in the Japanese population, except for CYP3A4 and CYP2C19. In this study, we evaluated the CYP2D6 metabolic capacity by measurement of CYP2D6 mRNA and protein levels and activity in the small intestine of Japanese individuals...
June 14, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28614988/in-vitro-inhibitory-effects-of-dihydromyricetin-on-human-liver-cytochrome-p450-enzymes
#2
Lu Liu, Sen Sun, Hongbing Rui, Xiaohua Li
CONTEXT: Dihydromyricetin (DHM) is the most abundant and active flavonoid component isolated from Ampelopsis grossedentata (Hand-Mazz) W.T. Wang (Vitaceae) and it possesses numerous pharmacological activities. However, whether DHM affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. MATERIALS AND METHODS: The inhibitory effects of DHM on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs)...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28606510/in-vitro-inhibitory-mechanisms-and-molecular-docking-of-1-s-1-acetoxychavicol-acetate-on-human-cytochrome-p450-enzymes
#3
A K M Mahmudul Haque, Kok Hoong Leong, Yoke Lin Lo, Khalijah Awang, Noor Hasima Nagoor
BACKGROUND: The compound, 1'-S-1'-acetoxychavicol acetate (ACA), isolated from the rhizomes of a Malaysian ethno-medicinal plant, Alpinia conchigera Griff. (Zingiberaceae), was previously shown to have potential in vivo antitumour activities. In the development of a new drug entity, potential interactions of the compound with the cytochrome P450 superfamily metabolizing enzymes need to be ascertain. PURPOSE: The concomitant use of therapeutic drugs may cause potential drug-drug interactions by decreasing or increasing plasma levels of the administered drugs, leading to a suboptimal clinical efficacy or a higher risk of toxicity...
July 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28606035/potential-minor-haplotypes-of-cyp2d6-in-the-japanese-population
#4
Masatoshi Masuda, Tsutomu Fujiwara, Masayuki Matsunaga, Takehisa Matsumaru
BACKGROUND: CYP2D6 is one of the most significant polymorphic genes of drug-metabolizing enzymes due to its association with different metabolic activities and the pharmacokinetics of CYP2D6 substrates. OBJECTIVE: The objective of this study was to explore for a novel haplotype of CYP2D6 in the Japanese population by using a large database of previous clinical studies. METHODS: We analyzed CYP2D6 genotype data from a total of 723 Japanese individuals for 8 loci (100C>T, 1758G>A, 1846G>A, 2573 insertion of C, 2850C>T, 2988G>A, 4125 insertion of 9bp, and 4180G>C) and gene deletion...
June 12, 2017: Drug Metabolism Letters
https://www.readbyqxmd.com/read/28594282/availability-of-cyp2d6-genotyping-results-in-general-practitioner-and-community-pharmacy-medical-records
#5
Mirjam Simoons, Hans Mulder, Robert A Schoevers, Henricus G Ruhé, Eric N van Roon
AIM: To investigate the availability of CYP450-2D6 (CYP2D6) genotyping results in general practitioner (GP) and/or community pharmacy records, and the influence thereof on psychotropic CYP2D6 substrate dosing. MATERIALS & METHODS: Primary outcome was the percentage of patients genotyped for CYP2D6 with their genotype/phenotype registered in GP and/or pharmacy records. Secondary outcome was the number of defined daily doses of psychotropic CYP2D6 substrates prescribed after genotyping...
June 8, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28593824/should-cyp2d6-be-genotyped-when-treating-with-tamoxifen
#6
Marzia Del Re, Eleonora Rofi, Valentina Citi, Leonardo Fidilio, Romano Danesi
Letter in regards to: Del Re M, Rofi E, Citi V, Fidilio L, Danesi R. Should CYP2D6 be genotyped when treating with tamoxifen? Pharmacogenomics 17(18), 1967-1969 (2016). In response to: Damkier P. Don't think twice it's all right: tamoxifen and CYP2D6 genotyping in the treatment of breast cancer patients. Pharmacogenomics 18(8), XXX (2017).
June 8, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28592184/don-t-think-twice-it-s-all-right-tamoxifen-and-cyp2d6-genotyping-in-the-treatment-of-breast-cancer-patients
#7
Per Damkier
Letter in resonse to: Del Re M, Rofi E, Citi V, Fidilio L, Danesi R. Should CYP2D6 be genotyped when treating with tamoxifen? Pharmacogenomics 17(18), 1967-1969 (2016).
June 8, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28589543/beta-blocker-use-and-fall-risk-in-older-individuals-original-results-from-two-studies-with-meta-analysis
#8
Annelies C Ham, Suzanne C van Dijk, Karin M A Swart, Anke W Enneman, Nikita L van der Zwaluw, Elske M Brouwer-Brolsma, Natasja M van Schoor, M Carola Zillikens, Paul Lips, Lisette C P G M de Groot, Albert Hofman, Renger F Witkamp, André G Uitterlinden, Bruno H Stricker, Nathalie van der Velde
AIMS: To investigate the association between use of beta-blockers and beta-blocker characteristics - selectivity, lipid solubility, intrinsic sympathetic activity (ISA), and CYP2D6 enzyme metabolism - and fall risk. METHODS: Data from two prospective studies were used, including community-dwelling individuals, N=7,662 (the Rotterdam Study) and 2,407 (B-PROOF), all aged ≥55 years. Fall incidents were recorded prospectively. Time-varying beta-blocker use was determined using pharmacy dispensing records...
June 7, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28558712/molecular-and-immunological-analyses-of-confirmed-plasmodium-vivax-relapse-episodes
#9
Sarunya Maneerattanasak, Panita Gosi, Srivicha Krudsood, Pattamawan Chimma, Jarinee Tongshoob, Yuvadee Mahakunkijcharoen, Chonlaphat Sukasem, Mallika Imwong, Georges Snounou, Srisin Khusmith
BACKGROUND: Relapse infections resulting from the activation hypnozoites produced by Plasmodium vivax and Plasmodium ovale represent an important obstacle to the successful control of these species. A single licensed drug, primaquine is available to eliminate these liver dormant forms. To date, investigations of vivax relapse infections have been few in number. RESULTS: Genotyping, based on polymorphic regions of two genes (Pvmsp1F3 and Pvcsp) and four microsatellite markers (MS3...
May 30, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28552654/microrna-hsa-mir-370-3p-suppresses-the-expression-and-induction-of-cyp2d6-by-facilitating-mrna-degradation
#10
Linjuan Zeng, Yinting Chen, Yong Wang, Li-Rong Yu, Bridgett Knox, Jiwei Chen, Tieliu Shi, Si Chen, Zhen Ren, Lei Guo, Yuanfeng Wu, David Liu, Kaihong Huang, Weida Tong, Dianke Yu, Baitang Ning
Cytochrome P450 2D6 (CYP2D6) participates in the metabolism of approximately 20-25% of prescribed drugs. Genetic polymorphisms influence the expression and/or activity of CYP2D6, and inter-individual differences in drug activation and elimination caused by CYP2D6 genetic variants were reported. However, little is known about the potential modulation of CYP2D6 expression by microRNAs (miRNAs). In the current study, by using in silico prediction of the stabilities of miRNA/mRNA complexes, we screened 38 miRNA candidates that may interact with the transcript of CYP2D6...
May 25, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28540639/exploiting-pharmacokinetic-models-of-tamoxifen-and-endoxifen-to-identify-factors-causing-subtherapeutic-concentrations-in-breast-cancer-patients
#11
Lena Klopp-Schulze, Markus Joerger, Sebastian G Wicha, Rob Ter Heine, Chantal Csajka, Zinnia P Parra-Guillen, Charlotte Kloft
BACKGROUND AND OBJECTIVES: A better understanding of the highly variable pharmacokinetics (PK) of tamoxifen and its active metabolite endoxifen in breast cancer patients is crucial to support individualised treatment. This study used a modelling and simulation approach to quantitatively assess the influence of cytochrome P450 (CYP) 2D6 activity and other relevant factors on tamoxifen and endoxifen PK to identify subgroups at risk for subtherapeutic endoxifen concentrations. METHODS: Simulations were performed using two previously published PK models jointly describing tamoxifen and endoxifen with CYP2D6 and CYP3A4/5 enzyme activities implemented as covariates...
May 24, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28526150/pharmacogenomics-in-pain-management
#12
REVIEW
Ramsey Saba, Alan D Kaye, Richard D Urman
There is interpatient variability to analgesic administration. Much can be traced to pharmacogenomics variations between individuals. Certain ethnicities are more prone to reduced function of CYP2D6. Weak opioids are subject to interpatient variation based on their CYP2D6 type. Strong opioids have variations based on their transport and individual metabolism. Several cytochrome enzymes have been found to be involved with ketamine but there is no strong evidence of individual polymorphisms manifesting in clinical outcomes...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28526056/the-blood-schizonticidal-activity-of-tafenoquine-makes-an-essential-contribution-to-its-prophylactic-efficacy-in-nonimmune-subjects-at-the-intended-dose-200%C3%A2-mg
#13
REVIEW
Geoffrey Dow, Bryan Smith
Tafenoquine (TQ) is an 8-aminoquinoline anti-malarial being developed for malaria prophylaxis. It has been generally assumed that TQ, administered prophylactically, acts primarily on the developing exoerythrocytic stages of malaria parasites (causal prophylaxis), and that polymorphisms in metabolic enzymes thought to impact the activity of other 8-aminoquinolines also inhibit this property of TQ. Furthermore, it has been suggested that a diagnostic test for CYP2D6 metabolizer status might be required. In field studies in which metabolic status was not an exclusion criteria, TQ has been shown to exhibit similar prophylactic efficacy as blood schizonticidal drugs (mefloquine)...
May 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28525288/inference-of-the-genetic-polymorphisms-of-cyp2d6-in-six-subtribes-of-the-malaysian-orang-asli-from-whole-genome-sequencing-data
#14
Choo Yee Yu, Geik Yong Ang, Vinothini Subramaniam, Richard Johari James, Aminuddin Ahmad, Thuhairah Abdul Rahman, Fadzilah Mohd Nor, Syahrul Azlin Shaari, Lay Kek Teh, Mohd Zaki Salleh
AIMS: CYP2D6 is one of the major enzymes in the cytochrome P450 monooxygenase system. It metabolizes ∼25% of prescribed drugs and hence, the genetic diversity of CYP2D6 gene has continued to be of great interest to the medical and pharmaceutical industries. This study aims to perform a systematic analysis of the CYP2D6 gene in six subtribes of the Malaysian Orang Asli. METHODS: Genomic DNAs were extracted from the blood samples followed by whole-genome sequencing...
May 19, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28522373/population-pharmacokinetics-of-carvedilol-enantiomers-and-their-metabolites-in-type-2-diabetes-and-healthy-subjects
#15
Glauco H B Nardotto, Vera L Lanchote, Eduardo B Coelho, Oscar Della Pasqua
Carvedilol, a drug available as a racemic mixture, is eliminated as 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 the 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/28515818/pharmacogenomic-testing-for-psychotropic-medication-selection-a-systematic-review-of-the-assurex-genesight-psychotropic-test
#16
(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/28512430/cyp2d6-phenotyping-using-urine-plasma-and-saliva-metabolic-ratios-to-assess-the-impact-of-cyp2d6-%C3%A2-10-on-interindividual-variation-in-a-chinese-population
#17
Rui Chen, Xin Zheng, Pei Hu
Purpose: Asian populations have around 40-60% frequency of reduced function allele CYP2D6(∗)10 compared to 1-2% in Caucasian populations. The wide range of CYP2D6 enzyme activities in subjects with the CYP2D6(∗)10 variant is a big concern for clinical practice. The quantitative analysis measuring the impact of CYP2D6 enzyme activity as a result of one CYP2D6(∗)10 allele or two CYP2D6(∗)10 alleles has not been reported in large Asian populations. Methods: A total of 421 healthy Chinese subjects were genotyped for CYP2D6 by polymerase chain reaction and direct DNA sequencing...
2017: Frontiers in Pharmacology
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
#18
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/28496987/effect-of-health-foods-on-cytochrome-p450-mediated-drug-metabolism
#19
Takamitsu Sasaki, Yu Sato, Takeshi Kumagai, Kouichi Yoshinari, Kiyoshi Nagata
BACKGROUND: Health foods have been widely sold and consumed in Japan. There has been an increase in reports of adverse effects in association with the expanding health food market. While health food-drug interactions are a particular concern from the viewpoint of safe and effective use of health foods, information regarding such interactions is limited owing to the lack of established methods to assess the effects of health food products on drug metabolism. We therefore developed cells that mimicked the activities of cytochrome P450 1A2 (CYP1A2), CYP2C9, CYP2C19, CYP2D6, and CYP3A4, which strongly contribute to drug metabolism in human hepatocytes, and established a system to assess the inhibitory activity of health foods toward P450-mediated metabolism...
2017: Journal of Pharmaceutical Health Care and Sciences
https://www.readbyqxmd.com/read/28489395/identification-of-potent-and-selective-cyp1a1-inhibitors-via-combined-ligand-and-structure-based-virtual-screening-and-their-in-vitro-validation-in-sacchrosomes-and-live-human-cells
#20
Prashant Joshi, Glen J P McCann, Vinay Sonawane, Ram A Vishwakarma, Bhabatosh Chaudhuri, Sandip B Bharate
Target structure-guided virtual screening (VS) is a versatile, powerful and inexpensive alternative to experimental high-throughput screening (HTS). In order to discover potent CYP1A1 enzyme inhibitors for cancer chemoprevention, a commercially library of 50,000 small molecules was utilized for VS guided by both ligand and structure-based strategies. For experimental validation, 300 ligands were proposed based on combined analysis of fitness scores from ligand based e-pharmacophore screening and docking score, prime MMGB/SA binding affinity and interaction pattern analysis from structure-based VS...
May 10, 2017: Journal of Chemical Information and Modeling
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