keyword
MENU ▼
Read by QxMD icon Read
search

Cyp2d6

keyword
https://www.readbyqxmd.com/read/28097507/in-vitro-phase-i-and-phase-ii-drug-metabolism-in-the-liver-of-juvenile-and-adult-g%C3%A3-ttingen-minipigs
#1
Els Van Peer, Frank Jacobs, Jan Snoeys, Jos Van Houdt, Ils Pijpers, Christophe Casteleyn, Chris Van Ginneken, Steven Van Cruchten
PURPOSE: In view of pediatric drug development, juvenile animal studies are gaining importance. However, data on drug metabolizing capacities of juvenile animals are scarce, especially in non-rodent species. Therefore, we aimed to characterize the in vitro biotransformation of four human CYP450 substrates and one UGT substrate in the livers of developing Göttingen minipigs. METHODS: Liver microsomes from late fetal, Day 1, Day 3, Day 7, Day 28, and adult male and female Göttingen minipigs were incubated with a cocktail of CYP450 substrates, including phenacetin, tolbutamide, dextromethorphan, and midazolam...
January 17, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28087463/effect-of-22-cyp2d6-variants-found-in-the-chinese-population-on-tolterodine-metabolism-in-vitro
#2
Hao Wang, Da-Peng Dai, Peng Sun, Li-Ping Xu, Bing-Qing Liang, Jian-Ping Cai, Guo-Xin Hu
Cytochrome P450 2D6 (CYP2D6) is an important member of the cytochrome P450 enzyme superfamily. We recently identified 22 novel variants in the Chinese population using PCR and bidirectional sequencing methods. The aim of this study is to characterize the enzymatic activity of these variants and their effects on the metabolism of the antimuscarinic drug tolterodine in vitro. A baculovirus-mediated expression system was used to express wild-type CYP2D6 and 24 variants (CYP2D6*2, CYP2D6*10, and 22 novel CYP2D6 variants) at high levels...
January 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28087064/effect-of-cyp2d6-polymorphisms-on-the-pharmacokinetics-of-propafenone-and-its-two-main-metabolites
#3
Mohammad-Reza Rouini, Minoo Afshar
AIM OF THE STUDY: Propafenone (PPF) is an antiarrhythmic drug, metabolized mainly by CYP2D6 to 5-hydroxypropafenone (5OH-PPF) and by CYP3A4 to norpropafenone (NOR-PPF). CYP2D6 shows a high degree of genetic polymorphism which is associated with diminished antiarrhythmic efficacy or cardiac seizures/cardiotoxicity. This study aimed to investigate the effect of the CYP2D6 polymorphism on the pharmacokinetics of PPF and its two main metabolites. The usefulness of PPF/5OH-PPF ratio for CYP2D6 phenotyping in healthy adults was also evaluated...
December 19, 2016: Thérapie
https://www.readbyqxmd.com/read/28074989/-antidepressants-agents-in-breast-cancer-patients-using-tamoxifen-review-of-basic-and-clinical-evidence
#4
María Elisa Irarrázaval O, Leonardo Gaete G
Tamoxifen (Tmf), is a standard of care for women with estrogen receptor positive (ER+) breast cancer. Endoxifen is a Tmf metabolite generated by cytochrome P450 2D6 (CYP2D6). Antidepressive agents (AD) are often prescribed to women with breast cancer not only for depression, but also for anxiety and hot flashes. Some AD are substrates or inhibitors of the Tmf metabolic pathway. Therefore there may be interactions when Tmf and AD are prescribed simultaneously. Oncologic protection afforded by Tmf may become less effective or null when AD are indicated, especially in poor metabolizing patients...
October 2016: Revista Médica de Chile
https://www.readbyqxmd.com/read/28074333/rosiglitazone-metabolism-in-human-liver-microsomes-using-a-substrate-depletion-method
#5
Maryam Bazargan, David J R Foster, Andrew K Davey, Beverly S Muhlhausler
BACKGROUND: Elimination of rosiglitazone in humans is via hepatic metabolism. The existing studies suggest that CYP2C8 is the major enzyme responsible, with a minor contribution from CYP2C9; however, other studies suggest the involvement of additional cytochrome P450 enzymes and metabolic pathways. Thus a full picture of rosiglitazone metabolism is unclear. OBJECTIVE: This study aimed to improve the current understanding of potential drug-drug interactions and implications for therapy by evaluating the kinetics of rosiglitazone metabolism and examining the impact of specific inhibitors on its metabolism using the substrate depletion method...
January 10, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28073119/in-vitro-inhibition-of-human-cyp450s-1a2-2c9-3a4-5-2d6-and-2e1-by-grandisin
#6
Maísa Daniela Habenschus, Fernanda de Lima Moreira, Norberto Peporine Lopes, Anderson R M de Oliveira
Grandisin, a lignan isolated from many species of plants, such as Virola surinamensis, is a potential drug candidate due to its biological properties, highlighted by its antitumor and trypanocidal activities. In this study, the inhibitory effects of grandisin on the activities of human cytochrome P450 enzymes were investigated by using human liver microsomes. Results showed that grandisin is a competitive inhibitor of CYP2C9 and a competitive and mechanism-based inhibitor of CYP3A4/5. The apparent Ki value for CYP2C9 was 50...
January 10, 2017: Planta Medica
https://www.readbyqxmd.com/read/28070879/a-review-of-pharmacogenetics-of-antimalarials-and-associated-clinical-implications
#7
REVIEW
Hazem Elewa, Kyle John Wilby
Genetic variability in drug-metabolizing enzymes and drug transporters is known to influence the pharmacokinetics of many drugs. Antimalarial drugs are a class of agents known to utilize metabolic and elimination pathways prone to genetic variation. This paper aims to review the genetic variants affecting antimalarial medications and discuss their clinical implications. Data were identified for the genes coding for the cytochrome P450 (CYP) enzymes: CYP2C8, CYP2C19, CYP2A6, CYP2D6, CYP2B6, and the P-glycoprotein drug transporter...
January 9, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28055020/participant-perceived-understanding-and-perspectives-on-pharmacogenomics-the-mayo-clinic-right-protocol-right-drug-right-dose-right-time
#8
Janet E Olson, Carolyn R Rohrer Vitek, Elizabeth J Bell, Michaela E McGree, Debra J Jacobson, Jennifer L St Sauver, Pedro J Caraballo, Joan M Griffin, Veronique L Roger, Suzette J Bielinski
PURPOSE: To examine predictors of understanding preemptive CYP2D6 pharmacogenomics test results and to identify key features required to improve future educational efforts of preemptive pharmacogenomics testing. METHODS: One thousand ten participants were surveyed after receiving preemptive CYP2D6 pharmacogenomics test results. RESULTS: Eighty-six percent (n = 869) of patients responded. Of the responders, 98% were white and 55% were female; 57% had 4 years or more of post-secondary education and an average age of 58...
January 5, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28052106/a-prediction-algorithm-for-drug-response-in-patients-with-mesial-temporal-lobe-epilepsy-based-on-clinical-and-genetic-information
#9
Mariana S Silva-Alves, Rodrigo Secolin, Benilton S Carvalho, Clarissa L Yasuda, Elizabeth Bilevicius, Marina K M Alvim, Renato O Santos, Claudia V Maurer-Morelli, Fernando Cendes, Iscia Lopes-Cendes
Mesial temporal lobe epilepsy is the most common form of adult epilepsy in surgical series. Currently, the only characteristic used to predict poor response to clinical treatment in this syndrome is the presence of hippocampal sclerosis. Single nucleotide polymorphisms (SNPs) located in genes encoding drug transporter and metabolism proteins could influence response to therapy. Therefore, we aimed to evaluate whether combining information from clinical variables as well as SNPs in candidate genes could improve the accuracy of predicting response to drug therapy in patients with mesial temporal lobe epilepsy...
2017: PloS One
https://www.readbyqxmd.com/read/28050713/metabolic-profiling-of-human-long-term-liver-models-and-hepatic-clearance-predictions-from-in-vitro-data-using-nonlinear-mixed-effects-modeling
#10
Nicole A Kratochwil, Christophe Meille, Stephen Fowler, Florian Klammers, Aynur Ekiciler, Birgit Molitor, Sandrine Simon, Isabelle Walter, Claudia McGinnis, Johanna Walther, Brian Leonard, Miriam Triyatni, Hassan Javanbakht, Christoph Funk, Franz Schuler, Thierry Lavé, Neil J Parrott
Early prediction of human clearance is often challenging, in particular for the growing number of low-clearance compounds. Long-term in vitro models have been developed which enable sophisticated hepatic drug disposition studies and improved clearance predictions. Here, the cell line HepG2, iPSC-derived hepatocytes (iCell®), the hepatic stem cell line HepaRG™, and human hepatocyte co-cultures (HμREL™ and HepatoPac®) were compared to primary hepatocyte suspension cultures with respect to their key metabolic activities...
January 3, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28046094/analysis-of-genetic-variation-in-cyp450-genes-for-clinical-implementation
#11
Liuh Ling Goh, Chia Wei Lim, Wey Cheng Sim, Li Xian Toh, Khai Pang Leong
BACKGROUND: Genetic determinants of drug response remain stable throughout life and offer great promise to patient-tailored drug therapy. The adoption of pharmacogenetic (PGx) testing in patient care requires accurate, cost effective and rapid genotyping with clear guidance on the use of the results. Hence, we evaluated a 32 SNPs panel for implementing PGx testing in clinical laboratories. METHODS: We designed a 32-SNP panel for PGx testing in clinical laboratories...
2017: PloS One
https://www.readbyqxmd.com/read/28044414/flexible-and-scalable-full-length-cyp2d6-long-amplicon-pacbio-sequencing
#12
Henk P J Buermans, Rolf H A M Vossen, Seyed Yahya Anvar, William G Allard, Henk-Jan Guchelaar, Stefan J White, Johan T den Dunnen, Jesse J Swen, Tahar van der Straaten
Cytochrome P450 2D6 (CYP2D6) is among the most important genes involved in drug metabolism. Specific variants are associated with changes in the enzyme's amount and activity. Multiple technologies exist to determine these variants, like the AmpliChip CYP450 test, Taqman qPCR, or Second-Generation Sequencing, however, sequence homology between cytochrome P450 genes and pseudogene CYP2D7 impairs reliable CYP2D6 genotyping, and variant phasing cannot accurately be determined using these assays. To circumvent this, we sequenced CYP2D6 using the Pacific Biosciences RSII and obtained high-quality, full-length, phased CYP2D6 sequences, enabling accurate variant calling and haplotyping of the entire gene-locus including exonic, intronic, and upstream and downstream regions...
January 3, 2017: Human Mutation
https://www.readbyqxmd.com/read/28018697/self-limited-kleptomania-symptoms-as-a-side-effect-of-duloxetine
#13
Christopher W T Miller, Keith E Gallagher
Introduction. Impulse control disorders (ICDs) have been described as a side effect of dopamine agonists, frequently used in neurodegenerative conditions affecting the nigrostriatal pathway. Serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine) have dose-dependent differential affinity for monoaminergic transporters, inhibiting the dopamine transporter at higher doses, thus increasing availability of synaptic dopamine, with the potential for similar impulse control side effects. Case Presentation...
2016: Case Reports in Psychiatry
https://www.readbyqxmd.com/read/28018217/pharmacogenomic-study-reveals-new-variants-of-drug-metabolizing-enzyme-and-transporter-genes-associated-with-steady-state-plasma-concentrations-of-risperidone-and-9-hydroxyrisperidone-in-thai-autism-spectrum-disorder-patients
#14
Sadeep Medhasi, Darawan Pinthong, Ekawat Pasomsub, Natchaya Vanwong, Nattawat Ngamsamut, Apichaya Puangpetch, Monpat Chamnanphon, Yaowaluck Hongkaew, Jirawat Pratoomwun, Penkhae Limsila, Chonlaphat Sukasem
The present study sought to investigate the genetic variants in drug metabolizing enzyme and transporter (DMET) genes associated with steady-state plasma concentrations of risperidone among Thai autism spectrum disorder (ASD) patients. ASD patients taking risperidone for at least 1 month were enrolled for this pharmacogenomic study. Genotyping profile was obtained using Affymetrix DMET Plus array interrogating 1931 variants in 231 genes. Steady-state plasma risperidone and 9-hydroxyrisperidone were measured using liquid chromatography/tandem mass spectrometry assay...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28012025/antifibrotic-effects-of-carvedilol-and-impact-of-liver-fibrosis-on-carvedilol-pharmacokinetics-in-a-rat-model
#15
Ebtehal El-Demerdash, Somaia A Abdel-Sattar, Wesam M El-Bakly, Eman A Mohamed
BACKGROUND AND OBJECTIVES: Carvedilol is a drug of choice in treatment of portal hypertension. The present study was designed to elucidate the potential role of antifibrotic effects of carvedilol in improving hepatic efficiency and the carvedilol oral pharmacokinetic changes during induction of liver fibrosis. METHODS: Rats were given CCl4 (1 ml/kg, intraperitoneal) twice weekly for 6 weeks and/or co-treated with carvedilol (10 mg/kg, orally) three times weekly on alternating days...
December 23, 2016: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28007398/development-of-gc-ms-based-cytochrome-p450-assay-for-the-investigation-of-multi-herb-interaction
#16
Hyun-A Oh, Hyunbeom Lee, Donghak Kim, Byung Hwa Jung
As drug interactions with cytochrome P450 enzymes become increasingly important in the field of drug discovery, a high-throughput screening method for analysing the effects of a drug is needed. We have developed a simple and rapid simultaneous analytical method using a cocktail approach for measuring the activities of seven cytochrome P450 enzymes (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4). Human liver microsomes were used as a source for the seven cytochrome P450 enzymes, and a gas chromatography-mass spectrometry (GC-MS) was used for analysing their activities...
February 15, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28006013/procarcinogens-determination-and-evaluation-by-yeast-based-biosensor-transformed-with-plasmids-incorporating-rad54-reporter-construct-and-cytochrome-p450-genes
#17
Van Ngoc Bui, Thi Thu Huyen Nguyen, Chi Thanh Mai, Yvan Bettarel, Thi Yen Hoang, Thi Thuy Linh Trinh, Nam Hai Truong, Hoang Ha Chu, Vu Thanh Thanh Nguyen, Huu Duc Nguyen, Stefan Wölfl
In Vietnam, a great number of toxic substances, including carcinogens and procarcinogens, from industrial and agricultural activities, food production, and healthcare services are daily released into the environment. In the present study, we report the development of novel yeast-based biosensor systems to determine both genotoxic carcinogens and procarcinogens by cotransformation with two plasmids. One plasmid is carrying human CPR and CYP (CYP3A4, CYP2B6, or CYP2D6) genes, while the other contains the RAD54-GFP reporter construct...
2016: PloS One
https://www.readbyqxmd.com/read/28002639/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-cyp2d6-genotype-and-use-of-ondansetron-and-tropisetron
#18
Gillian C Bell, Kelly E Caudle, Michelle Whirl-Carrillo, Ronald J Gordon, Keiko Hikino, Cynthia A Prows, Andrea Gaedigk, Jose A G Agundez, Senthilkumar Sadhasivam, Teri E Klein, Matthias Schwab
5-hydroxytryptamine type 3 (5-HT3 ) receptor antagonists are used in the prevention of chemotherapy- induced, radiation-induced and postoperative nausea and vomiting. CYP2D6 polymorphisms can influence the metabolism of some of these drugs (i.e. ondansetron and tropisetron) thereby affecting drug efficacy. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for ondansetron and tropisetron based on CYP2D6 genotype (updates at www.pharmgkb...
December 21, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27997040/clinical-pharmacogenetics-implementation-consortium-guideline-cpic%C3%A2-for-cyp2d6-and-cyp2c19-genotypes-and-dosing-of-tricyclic-antidepressants-2016-update
#19
J Kevin Hicks, Katrin Sangkuhl, Jesse J Swen, Vicki L Ellingrod, Daniel J Müller, Kazutaka Shimoda, Jeffrey R Bishop, Evan D Kharasch, Todd C Skaar, Andrea Gaedigk, Henry M Dunnenberger, Teri E Klein, Kelly E Caudle, Julia C Stingl
CYP2D6 and CYP2C19 polymorphisms affect the exposure, efficacy and safety of tricyclic antidepressants (TCAs), with some drugs being affected by CYP2D6 only (e.g., nortriptyline and desipramine) and others by both polymorphic enzymes (e.g., amitriptyline, clomipramine, doxepin, imipramine, and trimipramine). Evidence is presented for CYP2D6 and CYP2C19 genotype-directed dosing of TCAs. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants...
December 20, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27988492/cytochrome-p-450-2d6-cyp2d6-genotype-and-breast-cancer-recurrence-in-tamoxifen-treated-patients-evaluating-the-importance-of-loss-of-heterozygosity
#20
Thomas P Ahern, Daniel L Hertz, Per Damkier, Bent Ejlertsen, Stephen J Hamilton-Dutoit, James M Rae, Meredith M Regan, Alastair M Thompson, Timothy L Lash, Deirdre P Cronin-Fenton
Tamoxifen therapy for estrogen receptor-positive breast cancer reduces the risk of recurrence by approximately one-half. Cytochrome P-450 2D6, encoded by the polymorphic cytochrome P-450 2D6 gene (CYP2D6), oxidizes tamoxifen to its most active metabolites. Steady-state concentrations of endoxifen (4-hydroxy-N-desmethyltamoxifen), the most potent antiestrogenic metabolite, are reduced in women whose CYP2D6 genotypes confer poor enzyme function. Thirty-one studies of the association of CYP2D6 genotype with breast cancer survival have yielded heterogeneous results...
December 17, 2016: American Journal of Epidemiology
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"