Read by QxMD icon Read


Vinicius A Sortica, Juliana D Lindenau, Maristela G Cunha, Maria DO Ohnishi, Ana Maria R Ventura, Ândrea Kc Ribeiro-Dos-Santos, Sidney Eb Santos, Luciano Sp Guimarães, Mara H Hutz
BACKGROUND: Chloroquine/primaquine is the current therapy to eliminate Plasmodium vivax infection in the Amazon region. AIMS: This study investigates CYP1A2, CYP2C8, CYP2C9, CYP3A4 and CYP3A5 genetic polymorphisms influence on cloroquine/primaquine treatment. PATIENTS & METHODS: Generalized estimating equations analyses were performed to determine the genetic influence in parasitemia and/or gametocytemia clearance over treatment time in 164 patients...
October 21, 2016: Pharmacogenomics
Laureen A Lammers, Roos Achterbergh, Marcel C M Pistorius, Yuma Bijleveld, Emmely M de Vries, Anita Boelen, Heinz-Josef Klümpen, Johannes A Romijn, RonA A Mathôt
BACKGROUND: The metabolic activity of P450 enzymes in vivo can be determined by using selective probe drugs. The simultaneous administration of multiple CYP-specific probe drugs is commonly referred to as the "cocktail approach." Disadvantages of a cocktail are large volumes of samples required for analysis and time-consuming analyses. The aim of this study was to develop and validate a simplified but sensitive method for the simultaneous quantification of five probe drugs (caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A4), omeprazole (CYP2C19), and S-warfarin (CYP2C9)) in a previously validated cocktail using an LC-MS/MS method...
October 19, 2016: Therapeutic Drug Monitoring
Ling Xue, Nick Holford, Xiao-Liang Ding, Zhen-Ya Shen, Chen-Rong Huang, Hua Zhang, Jing-Jing Zhang, Zhe-Ning Guo, Cheng Xie, Ling Zhou, Zhi-Yao Chen, Lin-Sheng Liu, Li-Yan Miao
AIMS: The aims of this study are to apply a theory based mechanistic model to describe the pharmacokinetics (PK) and pharmacodynamics (PD) of S- and R-warfarin. METHODS: Clinical data were obtained from 264 patients. Total concentrations for S- and R-warfarin were measured by ultra-high performance liquid tandem mass spectrometry. Genotypes were measured using pyrosequencing. A sequential population pharmacokinetic parameter with data method was used to describe the international normalized ratio (INR) time course...
October 20, 2016: British Journal of Clinical Pharmacology
Susanne Hafner, Sabine Haubensak, Tanusree Paul, Oliver Zolk
Background | Differences (polymorphisms) in genes encoding drug targets, drug transport proteins, or drug metabolizing enzymes may be responsible, among other factors, for the observed variation in patients' responses to medications. The field of pharmacogenetics aims to identify patients at higher genetically-determined risk of adverse effects or poor response to medication. This information would allow for modification of dosage or substitution with alternative therapy. However, there is a lack of awareness of pharmacogenetic clinical practise guidelines...
October 2016: Deutsche Medizinische Wochenschrift
Dal-Sik Kim, Yunjeong Kim, Ji-Young Jeon, Min-Gul Kim
BACKGROUND: We evaluated the drug interaction profile of Red Ginseng (RG) with respect to the activities of major cytochrome P450 (CYP) enzymes and the drug transporter P-glycoprotein (P-gp) in healthy Korean volunteers. METHODS: This article describes an open-label, crossover study. CYP probe cocktail drugs, caffeine, losartan, dextromethorphan, omeprazole, midazolam, and fexofenadine were administered before and after RG supplementation for 2 wk. Plasma samples were collected, and tolerability was assessed...
October 2016: Journal of Ginseng Research
Koroush Khalighi, Gang Cheng, Seyedabbas Mirabbasi, Bahar Khalighi, Yin Wu, Wuqiang Fan
Warfarin therapy is complicated by its large inter-individual and intra-individual variability. Both genetic and non-genetic factors can affect warfarin therapy. This study aims to investigate the allele distribution of VKORC1, CYP2C9 and CYP2C19, contribution of different allele variants and possible gene-gene interaction on warfarin therapy. Four hundreds and ninety-two patients were enrolled and single nucleotide polymorphisms for vitamin K epoxide reductase complex subunit 1 (VKORC1), cytochrome P450 CYP2C9 and cytochrome P450 CYP2C19 were genotyped...
October 14, 2016: Journal of Thrombosis and Thrombolysis
Isabel López, Estela Sangüesa, Yves Vancraenendonck, Estefanía Zuriaga, María Pilar Ribate, Cristina Belén García
Vitamin K antagonists are highly effective antithrombotic drugs. However, appropriate dosing is difficult to establish owing to its narrow therapeutic window as well as widespread inter- and intra-individual variability in dosage. Compared with dosing solely based on clinical information, pharmacogenetics can help improve the therapy with coumarins by decreasing the time to reach a stable dose and reducing the risk of bleeding. Most of the studies about genotyping of patients using vitamin K antagonists have focused on predicting the stable dose...
October 14, 2016: Drug Metabolism and Personalized Therapy
Zhiying Luo, Xi Li, Mingfeng Zhu, Jie Tang, Zhi Li, Xinming Zhou, Guobao Song, Zhaoqian Liu, Honghao Zhou, Wei Zhang
BACKGROUND: The variation among patients in warfarin response complicated the management of warfarin therapy, improper therapeutic dose usually result in serious adverse events. OBJECTIVE: A two-stage extreme phenotype strategy was conducted to discover novel warfarin dose associated mutations in heart valve replacement (HVR) patients. PATIENTS/METHOD: A total of 1617 warfarin stable dose (WSD) patients were enrolled and divided randomly into two cohorts...
October 14, 2016: Journal of Thrombosis and Haemostasis: JTH
Elena Puris, Markku Pasanen, Mikko Gynther, Merja R Häkkinen, Jussi Pihlajamäki, Tapani Keränen, Paavo Honkakoski, Hannu Raunio, Aleksanteri Petsalo
Cocktail phenotyping using specific probe drugs for cytochrome P450 (CYP) enzymes provides information on the real-time activity of multiple CYPs. We investigated different sample preparation techniques and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with simple protein precipitation for the analysis of nine CYP probe drugs and their metabolites in human serum and urine. Specific CYP probe drugs (melatonin, CYP1A2; nicotine, CYP2A6; bupropion, CYP2B6; repaglinide, CYP2C8; losartan, CYP2C9; omeprazole, CYP2C19 and CYP3A4; dextromethorphan, CYP2D6; chlorzoxazone, CYP2E; midazolam, CYP3A4) and their main metabolites, with the exception of 3'-hydroxyrepaglinide, were quantified in human serum and urine using the developed LC-MS/MS method...
October 12, 2016: Analytical and Bioanalytical Chemistry
Cheng Zhong, Hai-Yang Xie, Lin Zhou, Xiao Xu, Shu-Sen Zheng
BACKGROUND: Because of an increasing discrepancy between the number of potential liver graft recipients and the number of organs available, scientists are trying to create artificial liver to mimic normal liver function and therefore, to support the patient's liver when in dysfunction. 3D printing technique meets this purpose. The present study was to test the feasibility of 3D hydrogel scaffolds for liver engineering. METHODS: We fabricated 3D hydrogel scaffolds with a bioprinter...
October 2016: Hepatobiliary & Pancreatic Diseases International: HBPD INT
Martina Štěpánková, Kristýna Krasulová, Aneta Dořičáková, Ondřej Kurka, Pavel Anzenbacher, Zdeněk Dvořák
Dihydropyridine calcium channel blockers (CCBs) are used as anti-hypertensives and in the treatment of angina pectoris. Structurally, CCBs have at least one chiral center in the molecule, thereby existing in two or more different enantiomers. In the current paper we examined effects of benidipine, felodipine and isradipine enantiomers on the expression and enzyme activities of human xenobiotics-metabolizing cytochromes P450. All CCBs dose-dependently activated aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR), as revealed by gene reporter assays...
October 9, 2016: Toxicology Letters
Allison B Chambliss, Molly Resnick, Athena K Petrides, William A Clarke, Mark A Marzinke
BACKGROUND: Current methods for the detection of single nucleotide polymorphisms (SNPs) associated with aberrant drug-metabolizing enzyme function are hindered by long turnaround times and specialized techniques and instrumentation. In this study, we describe the development and validation of a high-resolution melting (HRM) curve assay for the rapid screening of variant genotypes for targeted genetic polymorphisms in the cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP3A5. METHODS: Sequence-specific primers were custom-designed to flank nine SNPs within the genetic regions of aforementioned drug metabolizing enzymes...
October 12, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
İbrahim Ömer Barlas, Orhan Sezgin, Collet Dandara, Gözde Türköz, Emre Yengel, Zinhle Cindi, Handan Ankaralı, Semra Şardaş
Pharmacogenomics harnesses the utility of a patient's genome (n = 1) in decisions on which therapeutic drugs and in what amounts should be administered. Often, patients with shared ancestry present with comparable genetic profiles that predict drug response. However, populations are not static, thus, often, population mobility through migration, especially enmasse as is seen for refugees, changes the pharmacogenetic profiles of resultant populations and therefore observed responses to commonly used therapeutic drugs...
October 2016: Omics: a Journal of Integrative Biology
Hirotaka Amano, Daichi Kazamori, Kenji Itoh
Three major organosulfur compounds of aged garlic extract, S-allyl-L-cysteine (SAC), S-methyl-L-cysteine (SMC), and trans-S-1-propenyl-L-cysteine (S1PC), were examined for their effects on the activities of five major isoforms of human CYP enzymes: CYP1A2, 2C9, 2C19, 2D6, and 3A4. The metabolite formation from probe substrates for the CYP isoforms was examined in human liver microsomes in the presence of organosulfur compounds at 0.01-1 mM by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis...
2016: Biological & Pharmaceutical Bulletin
Shiv Bahadur, Pulok K Mukherjee, S K Milan Ahmmed, Amit Kar, Ranjit K Harwansh, Subrata Pandit
OBJECTIVE: Tinospora cordifolia is used for treatment of several diseases in Indian system of medicine. In the present study, the inhibition potential of T. cordifolia extracts and its constituent tinosporaside to cause herb-drug interactions through rat and human liver cytochrome enzymes was evaluated. MATERIALS AND METHODS: Bioactive compound was quantified through reverse phase high-performance liquid chromatography, to standardize the plant extracts and interaction potential of standardized extract...
September 2016: Indian Journal of Pharmacology
Yongjie Zhang, Nico P E Vermeulen, Jan N M Commandeur
AIMS: Oxidative bioactivation of amodiaquine (AQ) by cytochrome P450s to a reactive quinoneimine is considered as an important mechanism underlying its idiosyncratic hepatotoxicity. However, because internal exposure to its major metabolite N-desethylamodiaquine (DEAQ) is up to 240 fold higher than AQ, bioactivation of DEAQ might significant contribute to covalent binding. The aim of the present study was to compare the kinetics of bioactivation of AQ and DEAQ by human liver microsomes and to characterize the CYPs involved in bioactivation of AQ and DEAQ...
October 8, 2016: British Journal of Clinical Pharmacology
Viktoriia Starokozhko, Suresh Vatakuti, Bauke H Schievink, Marjolijn T Merema, Annika Asplund, Jane Synnergren, Anders Aspegren, Geny M M Groothuis
Human precision-cut liver slices (hPCLS) are a valuable ex vivo model that can be used in acute toxicity studies. However, a rapid decline in metabolic enzyme activity limits their use in studies that require a prolonged xenobiotic exposure. The aim of the study was to extend the viability and function of hPCLS to 5 days of incubation. hPCLS were incubated in two media developed for long-term culture of hepatocytes, RegeneMed(®), and Cellartis(®), and in the standard medium WME. Maintenance of phase I and II metabolism was studied both on gene expression as well as functional level using a mixture of CYP isoform-specific substrates...
October 7, 2016: Archives of Toxicology
L Zhang, Q Cai, R S Wiederkehr, M Fauvart, P Fiorini, B Majeed, M Tsukuda, T Matsuno, T Stakenborg
Pharmacogenetics has often been touted as a cornerstone for precision medicine as detailed knowledge of a specific genetic makeup may allow for accurate predictions of a patient's individual drug response. Still, the widespread use of genetic tests is limited as they remain expensive and cumbersome, requiring sophisticated tools and highly trained personnel. In order for pharmacogenetics to reach its full potential, more cost-effective and easily accessible genotyping methods are desired. To meet these challenges, we present a silicon-based integrated microsystem for the detection of multiple single nucleotide polymorphisms (SNPs) directly from human blood...
October 5, 2016: Lab on a Chip
Xianbao Shi, Brianna Mackie, Gang Zhang, Shuman Yang, Yonggui Song, Dan Su, Yali Liu, Lina Shan
Morusin, the important active component of a traditional Chinese medicine, Morus alba L., has been shown to exhibit many vital pharmacological activities. In this study, six recombinant CYP450 supersomes and liver microsomes were used to perform metabolic studies. Chemical inhibition studies and screening assays with recombinant human cytochrome P450s were also used to characterize the CYP450 isoforms involved in morusin metabolism. The morusin metabolites identified varied greatly among different species. Eight metabolites of morusin were detected in the liver microsomes from pigs (PLMs), rats (RLMs), and monkeys (MLMs) by LC-MS/MS and six metabolites were detected in the liver microsomes from humans (HLMs), rabbits (RAMs), and dogs (DLMs)...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Shilong Zhong, Weichao Han, Chuqi Hou, Junjin Liu, Lili Wu, Menghua Liu, Zhi Liang, Haoming Lin, Lili Zhou, Shuwen Liu, Lan Tang
Cytochrome P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) play important roles in the metabolism of exogenous and endogenous compounds. The gene transcription of CYPs and UGTs can be enhanced or reduced by transcription factors (TFs). This study aims to explore novel TFs involved in the regulatory network of human hepatic UGTs/CYPs. Correlations between the transcription levels of 683 key TFs and CYPs/UGTs in three different human liver expression profiles (n = 640) were calculated first. Supervised weighted correlation network analysis (sWGCNA) was employed to define hub genes among the selected TFs...
September 28, 2016: AAPS Journal
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"