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https://www.readbyqxmd.com/read/28526150/pharmacogenomics-in-pain-management
#1
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
#2
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
#3
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
#4
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
#5
(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
#6
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
#7
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...
May 16, 2017: Journal of Pain & Palliative Care Pharmacotherapy
https://www.readbyqxmd.com/read/28496987/effect-of-health-foods-on-cytochrome-p450-mediated-drug-metabolism
#8
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
#9
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
https://www.readbyqxmd.com/read/28484907/inhibition-of-cytochrome-p450-and-uridine-5-diphospho-glucuronosyltransferases-by-mam-2201-in-human-liver-microsomes
#10
Tae Yeon Kong, Ju-Hyun Kim, Soon-Sang Kwon, Jae Chul Cheong, Hee Seung Kim, Moon Kyo In, Hye Suk Lee
MAM-2201, a synthetic cannabinoid, is a potent agonist of the cannabinoid receptors and is increasingly used as an illicit recreational drug. The inhibitory effects of MAM-2201 on major drug-metabolizing enzymes such as cytochrome P450s (CYPs) and uridine 5'-diphospho-glucuronosyltransferases (UGTs) have not yet been investigated although it is widely abused, sometimes in combination with other drugs. We evaluated the inhibitory effects of MAM-2201 on eight major human CYPs (CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4) and six UGTs (UGTs 1A1, 1A3, 1A4, 1A6, 1A9, and 2B7) of pooled human liver microsomes; we thus explored potential MAM-2201-induced drug interactions...
May 8, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28480819/should-a-routine-genotyping-of-cyp2d6-and-cyp2c19-genetic-polymorphisms-be-recommended-to-predict-venlafaxine-efficacy-in-depressed-patients-treated-in-psychiatric-settings
#11
Adela Taranu, Romain Colle, Florence Gressier, Khalil El Asmar, Laurent Becquemont, Emmanuelle Corruble, Céline Verstuyft
AIM: The antidepressant venlafaxine (VEN) is metabolized by CYP2D6 and CYP2C19. The aim of this study was to assess the relevance of generalizing to daily practice the genotyping of CYP2D6 and CYP2C19 to predict VEN efficacy in depressed patients treated in psychiatric settings. PATIENTS & METHODS: This study was nested in a naturalistic cohort, with 206 patients requiring a new antidepressant treatment and genotyped for CYP2D6 *3, *4, *5 del, *6, *2xN, *10, *41 and CYP2C19 *2, *3, *4, *5, *17 alleles...
May 8, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28480783/pharmacogenetics-of-drug-drug-interaction-and-drug-drug-gene-interaction-a-systematic-review-on-cyp2c9-cyp2c19-and-cyp2d6
#12
Muh Akbar Bahar, Didik Setiawan, Eelko Hak, Bob Wilffert
Currently, most guidelines on drug-drug interaction (DDI) neither consider the potential effect of genetic polymorphism in the strength of the interaction nor do they account for the complex interaction caused by the combination of DDI and drug-gene interaction (DGI) where there are multiple biotransformation pathways, which is referred to as drug-drug-gene interaction (DDGI). In this systematic review, we report the impact of pharmacogenetics on DDI and DDGI in which three major drug-metabolizing enzymes - CYP2C9, CYP2C19 and CYP2D6 - are central...
May 8, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28475098/genetic-polymorphisms-of-cytochrome-p450-enzymes-cyp2c9-cyp2c19-cyp2d6-cyp3a4-and-cyp3a5-in-the-croatian-population
#13
Lana Ganoci, Tamara Božina, Nikica Mirošević Skvrce, Mila Lovrić, Petar Mas, Nada Božina
BACKGROUND: Data on the frequency of pharmacogenetic polymorphisms in the Croatian population are limited. We determined and analyzed frequencies for the most important CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 genetic variants in the Croatian population. METHODS: 2637 subjects were included. Genotyping was performed by real-time polymerase chain reaction (PCR) using TaqMan® DME or TaqMan® SNP Genotyping Assays, and by PCR, and PCR-RFLP analysis. RESULTS: For CYP2C9, allele frequencies of *2 and *3 variant were 14...
February 11, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28473326/reduced-carboxylesterase-1-is-associated-with-endothelial-injury-in-methamphetamine-induced-pulmonary-arterial-hypertension
#14
Mark E Orcholski, Artyom Khurshudyan, Elya A Shamskhou, Ke Yuan, Ian Y Chen, Sean D Kodani, Christophe Morisseau, Bruce D Hammock, Ellen M Hong, Ludmila Alexandrova, Tero-Pekka Alastalo, Gerald Berry, Roham T Zamanian, Vinicio A de Jesus Perez
Pulmonary arterial hypertension is a complication of methamphetamine use (METH-PAH) but the pathogenic mechanisms are unknown. Given that cytochrome P450 2D6 (CYP2D6) and carboxylesterase 1 (CES1) are involved in metabolism of METH and other amphetamine-like compounds, we postulated that loss of function variants could contribute to METH-PAH. While no difference in CYP2D6 expression was seen by lung immunofluorescence, CES1 expression was significantly reduced in endothelium of METH-PAH microvessels. Mass spectrometry analysis showed that healthy pulmonary microvascular endothelial cells (PMVECs) have the capacity to both internalize and metabolize METH...
May 4, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28470112/sequencing-the-cyp2d6-gene-from-variant-allele-discovery-to-clinical-pharmacogenetic-testing
#15
Yao Yang, Mariana R Botton, Erick R Scott, Stuart A Scott
CYP2D6 is one of the most studied enzymes in the field of pharmacogenetics. The CYP2D6 gene is highly polymorphic with over 100 catalogued star (*) alleles, and clinical CYP2D6 testing is increasingly accessible and supported by practice guidelines. However, the degree of variation at the CYP2D6 locus and homology with its pseudogenes make interrogating CYP2D6 by short-read sequencing challenging. Moreover, accurate prediction of CYP2D6 metabolizer status necessitates analysis of duplicated alleles when an increased copy number is detected...
May 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28470111/serum-clomipramine-and-desmethylclomipramine-levels-in-a-cyp2c19-and-cyp2d6-intermediate-metabolizer
#16
Jacob T Brown, Mark Schneiderhan, Seenae Eum, Jeffrey R Bishop
Pharmacogenetics within psychiatry has the potential to aid in the dose and selection of medications. A substantial number of psychiatric medications are metabolized through either of the highly polymorphic drug-metabolizing enzymes CYP2D6 and CYP2C19. Of these, clomipramine is subject to metabolism by both CYP2C19 and CYP2D6, leaving individuals with deficiencies of these drug-metabolizing enzymes at risk of higher concentrations of the parent molecule. Herein, we present the case of a 29-year-old male with diagnoses of depression and obsessive compulsive disorder who had trialed and failed a dozen psychiatric medications, many of which are subject to metabolism by CYP2D6 and/or CYP2C19, and had most recently been taking clomipramine for approximately 2...
May 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28470107/cyp450-genotype-and-aggressive-behavior-on-selective-serotonin-reuptake-inhibitors
#17
Corine Ekhart, Maja Matic, Agnes Kant, Eugène van Puijenbroek, Ron van Schaik
AIM: Genetic variants for selective serotonin reuptake inhibitor (SSRI) metabolizing enzymes have been hypothesized to be a risk factor for aggression as adverse drug effect of SSRIs. Our aim was to assess the possible involvement of these polymorphisms on aggression when using SSRIs. MATERIALS & METHODS: A retrospective noninterventional case-control study was performed on 18 cases. The genetic profile of two main genes involved in the metabolism of SSRIs was determined, and predicted phenotype frequencies were compared with Dutch controls and literature data...
May 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28468305/inhibitory-effects-of-dimethyllirioresinol-epimagnolin-a-eudesmin-fargesin-and-magnolin-on-cytochrome-p450-enzyme-activities-in-human-liver-microsomes
#18
Ju-Hyun Kim, Soon-Sang Kwon, Hyeon-Uk Jeong, Hye Suk Lee
Magnolin, epimagnolin A, dimethyllirioresinol, eudesmin, and fargesin are pharmacologically active tetrahydrofurofuranoid lignans found in Flos Magnoliae. The inhibitory potentials of dimethyllirioresinol, epimagnolin A, eudesmin, fargesin, and magnolin on eight major human cytochrome P450 (CYP) enzyme activities in human liver microsomes were evaluated using liquid chromatography-tandem mass spectrometry to determine the inhibition mechanisms and inhibition potency. Fargesin inhibited CYP2C9-catalyzed diclofenac 4'-hydroxylation with a Ki value of 16...
May 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28461741/functional-characterization-of-wild-type-and-24-cyp2d6-allelic-variants-on-gefitinib-metabolism-in-vitro
#19
Ping Fang, Xiang Zheng, Jiayang He, Honglei Ge, Pengfei Tang, Jianping Cai, Guoxin Hu
BACKGROUND: Cytochrome P450 2D6 (CYP2D6), a member of the CYP450 enzyme super family, is a polymorphic enzyme that metabolizes ~25% of therapeutic drugs. CYP2D6 exhibits significant genetic polymorphisms which might cause adverse effects and therapeutic failures of some drugs. OBJECTIVE: The purpose of this study was to evaluate the catalytic activities of 22 novel CYP2D6 alleles (CYP2D6*87, *88, *89, *90, *91, *92, *93, *94, *95, *96, *97, *98, R25Q, F164L, E215K, F219S, V327M, D336N, V342M, R344Q, R440C, R497C) on the metabolism of gefitinib in vitro...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28458572/pharmacogenetic-testing-revisited-5-nuclease-real-time-polymerase-chain-reaction-test-panels-for-genotyping-cyp2d6-and-cyp2c19
#20
Jens Borggaard Larsen, Jan Borg Rasmussen
Due to their involvement in the metabolization of commonly prescribed psychopharmaceutical drugs, the cytochrome oxidase genes CYP2D6 and CYP2C19 are extensive targets for pharmacogenetic testing. The existence of common allelic variants allows the prediction of a metabolic phenotype based on a genotype result, hereby supplying a clinical tool for optimizing prescription and minimizing adverse effects. In this study, we present the development of two 5' nuclease real-time polymerase chain reaction (PCR) test panels, capable of detecting eight of the most clinically relevant alleles of the CYP2D6 gene (*2, *3, *4, *6, *9, *10, 17, *41) and the three most common nonfunctional alleles of CYP2C19 (*2, *3, *4)...
2017: Pharmacogenomics and Personalized Medicine
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