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https://www.readbyqxmd.com/read/27922762/nonchemotherapy-drug-induced-agranulocytosis-in-children-detected-by-a-prospective-pharmacovigilance-program
#1
Nicolás Medrano-Casique, Hoi Y Tong, Alberto M Borobia, Antonio J Carcas, Jesús Frías, Elena Ramírez
OBJECTIVES: A prospective evaluation of nonchemotherapy drug-induced agranulocytosis (DIA) cases, which are infrequent in the pediatric population. We characterize agranulocytosis cases and assess lab test differences between drug- and nondrug-induced agranulocytosis. METHODS: Through our Prospective Pharmacovigilance Program from Laboratory Signals at Hospital we detected pediatric agranulocytosis cases from July 2007 to December 2010. This program estimates the incidence, drug causality, clinical features, outcomes of DIA pediatric cases, and assesses laboratory differences with respect to non-DIA...
December 6, 2016: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/27919396/think-time-a-novel-approach-to-analysis-of-clinicians-behavior-after-reduction-of-drug-drug-interaction-alerts
#2
Richard Schreiber, Julia A Gregoire, Jacob E Shaha, Steven H Shaha
OBJECTIVES: Pharmacologic interaction alerting offers the potential for safer medication prescribing, but research reveals persistent concerns regarding alert fatigue. Research studies have tried various strategies to resolve this problem, with low overall success. We examined the effects of targeted alert reduction on clinician behavior in a resource constrained hospital. METHODS: A physician and a pharmacy informaticist reduced alert levels of several drug-drug interactions (DDI) that clinicians almost always overrode with approval from and knowledge of the medical staff...
January 2017: International Journal of Medical Informatics
https://www.readbyqxmd.com/read/27917367/the-role-of-interaction-model-in-simulation-of-drug-interactions-and-qt-prolongation
#3
REVIEW
Barbara Wiśniowska, Sebastian Polak
Computational modelling is a cornerstone of Comprehensive In Vitro Proarrhythmia Assay and is re-increasingly being used in drug development. Electrophysiological effects of drug-drug interactions can be predicted in silico, e.g. with the use of in vitro cardiac ion channel data, PK profiles and human ventricular cardiomyocyte models. There are, however, several approaches with different assumptions used to assess the combined effect of multiple drugs, and there is no agreed standard interaction model. The aim of this study was to assess whether the choice of the drug-drug interaction (DDI) model (Bliss independence, Loewe additivity, or simple sum) influences the results of QT interval simulation trial...
2016: Current Pharmacology Reports
https://www.readbyqxmd.com/read/27910730/retrospective-use-of-pbpk-modelling-to-understand-a-clinical-drug-drug-interaction-between-dextromethorphan-and-gsk1034702
#4
Michael J Hobbs, Jackie Bloomer, Gordon Dear
: 1. PURPOSE: In a clinical trial, a strong drug-drug interaction (DDI) was observed between dextromethorphan (DM, the object or victim drug) and GSK1034702 (the precipitant or perpetrator drug), following single and repeat doses. This study determined the inhibition parameters of GSK1034702 in vitro and applied PBPK modelling approaches to simulate the clinical observations and provide mechanistic hypotheses to understand the DDI. 2. METHODS: In vitro assays were conducted to determine the inhibition parameters of human CYP2D6 by GSK1034702...
December 2, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27907909/egfr-kinase-inhibitors-and-gastric-acid-suppressants-in-egfr-mutant-nsclc-a-retrospective-database-analysis-of-potential-drug-interaction
#5
Nesaretnam Barr Kumarakulasinghe, Nicholas Syn, Yu Yang Soon, Atasha Asmat, Huili Zheng, En Yun Loy, Brendan Pang, Ross Andrew Soo
BACKGROUND: Erlotinib and gefitinib are weak base drugs whose absorption and clinical efficacy may be impaired by concomitant gastric acid suppressive (AS) therapy, yet proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2As) are widely indicated in non-small cell lung cancer (NSCLC) patients for the prevention and treatment of erlotinib-induced gastrointestinal injury and corticosteroid-associated gastric irritation. We assessed the clinical relevance of this potential drug-drug interaction (DDI) in a retrospective cohort of EGFR-mutant NSCLC patients...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27890005/mechanism-based-inhibitors-from-phytomedicine-risks-of-hepatotoxicity-and-their-potential-hepatotoxic-substructures
#6
Lili Wang, Xin He, Chunhuan Jin, Gregory Ondieki
The adverse reactions and side effects associated with use of herbal medicines, especially their damaging effects on the liver have increasingly been reported worldwide. Some of the herbal ingredients have the potential risk of herb-induced liver injury but their hepatotoxicity mechanisms and associated risk factors are not well characterized until now. Xenobiotics are catalyzed by cytochrome P450 enzymes into highly reactive metabolites, which can covalently bind to the enzyme itself and subsequently cause mechanism-based inhibition (MBI)...
November 23, 2016: Current Drug Metabolism
https://www.readbyqxmd.com/read/27889873/information-technology-based-interventions-to-improve-drug-drug-interaction-outcomes-a-systematic-review-on-features-and-effects
#7
Ehsan Nabovati, Hasan Vakili-Arki, Zhila Taherzadeh, Mohammad Reza Saberi, Stephanie Medlock, Ameen Abu-Hanna, Saeid Eslami
The purpose of this systematic review was to identify features and effects of information technology (IT)-based interventions on outcomes related to drug-drug interactions (DDI outcomes). A literature search was conducted in Medline, EMBASE, and the Cochrane Library for published English-language studies. Studies were included if a main outcome was related to DDIs, the intervention involved an IT-based system, and the study design was experimental or observational with controls. Study characteristics, including features and effects of IT-based interventions, were extracted...
January 2017: Journal of Medical Systems
https://www.readbyqxmd.com/read/27875918/expected-and-actual-adverse-drug-drug-interactions-in-elderly-patients-accessing-the-emergency-department-data-from-the-ancestral-ed-study
#8
A Marino, A Capogrosso-Sansone, M Tuccori, G Bini, V Calsolaro, S Mantarro, I Convertino, G Pasqualetti, E Orsitto, M Santini, F Monzani, C Blandizzi
OBJECTIVE: This study was aimed at evaluating the frequency and describing the adverse drug-drug interactions (DDIs) recorded among elderly patients accessing the emergency department (ED). METHODS: Patients aged ≥65 years, accessing the ED of Pisa University Hospital (Italy) from 1 January 2015 to 31 December 2015 within the ANCESTRAL-ED program, were included in this study. 'Expected' DDIs were assessed using Thomson Micromedex®. Each ED admission (discharge diagnosis) consistent with the signs and symptoms of an expected DDI for each patient was classified as an 'actual' DDI...
December 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27866079/multimodal-plasmonic-biosensing-nanostructures-prepared-by-dna-directed-immobilization-of-multifunctional-dna-gold-nanoparticles
#9
Nuria Tort, J-Pablo Salvador, M-Pilar Marco
Biofunctional multimodal plasmonic nanostructures suitable for multiplexed localized surface plasmon resonance (LSPR) biosensing have been created by DNA-directed immobilization (DDI) of two distinct multifunctional biohybrid gold nanoparticles. Gold nanoparticles (AuNP) of distinct sizes, and therefore showing distinct plasmon resonant peaks (RP), have been biofunctionalized and codified with two different single stranded-DNA (ssDNA) chains. One of these oligonucleotide chains has been specifically designed to direct each AuNP to a distinct location of the surface of a DNA microarray chip through specific hybridization with complementary oligonucleotide strands...
November 11, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27862160/in-vitro-and-pbpk-based-assessment-of-drug-drug-interaction-potential-of-canagliflozin
#10
Rao N V S Mamidi, Shannon Dallas, Carlo Sensenhauser, Heng Keang Lim, Ellen Scheers, Peter Verboven, Filip Cuyckens, Laurent Leclercq, David C Evans, Michael F Kelley, Mark D Johnson, Jan Snoeys
AIMS: Canagliflozin is a recently approved drug for use in the treatment of type 2 diabetes. The potential for canagliflozin to cause clinical drug-drug interactions (DDIs) was assessed. METHODS: DDI potential of canagliflozin was investigated using in vitro test systems containing drug metabolizing enzymes or transporters. Basic predictive approaches were applied to determine potential interaction in vivo. A physiologically-based pharmacokinetic (PBPK) model was developed and clinical DDI simulations were performed to determine the likelihood of CYP inhibition by canagliflozin...
November 11, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27858342/physiologically-based-pharmacokinetic-pbpk-modeling-of-pitavastatin-and-atorvastatin-to-predict-drug-drug-interactions-ddis
#11
Peng Duan, Ping Zhao, Lei Zhang
BACKGROUND: The disposition of statins varies and involves both metabolizing enzymes and transporters, making predictions of statin drug-drug interactions (DDIs) challenging. Physiologically based pharmacokinetic (PBPK) models have, however, demonstrated ability to predict complex DDIs. OBJECTIVE: In this study, PBPK models of two statins (pitavastatin and atorvastatin) were developed and applied to predict pitavastatin and atorvastatin associated DDIs. METHOD: Pitavastatin and atorvastatin PBPK models were developed using in vitro and human pharmacokinetic data in a population-based PBPK software (SimCYP(®)) by considering the contribution of both metabolizing enzymes and transporters to their overall pharmacokinetics...
November 17, 2016: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27854076/dodeca-2-e-4-e-dienoic-acid-isobutylamide-enhances-glucose-uptake-in-3t3-l1-cells-via-activation-of-akt-signaling
#12
Kyeong-Mi Choi, Wonkyun Kim, Jin Tae Hong, Hwan-Soo Yoo
Dodeca-2(E),4(E)-dienoic acid isobutylamide (DDI), an alkamide derived from the plant Echinacea purpurea, promotes adipocyte differentiation and activates peroxisome proliferator-activated receptor γ, which is associated with enhanced insulin sensitivity. In the present study, we investigated whether DDI may increase glucose uptake through activation of the insulin signaling pathway in 3T3-L1 adipocytes. DDI increased insulin-stimulated glucose uptake, and expression and translocation of glucose transporter 4 in adipocytes treated with sub-optimal levels of insulin...
November 16, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27853934/evaluation-of-in-vitro-cytochrome-p450-inhibition-and-in-vitro-fate-of-structurally-diverse-n-oxide-metabolites-case-studies-with-clozapine-levofloxacin-roflumilast-voriconazole-and-zopiclone
#13
Poonam Giri, Sneha Naidu, Nirmal Patel, Harilal Patel, Nuggehally R Srinivas
BACKGROUND AND OBJECTIVES: The role of metabolite(s) to elicit potential clinical drug-drug interaction (DDI) via cytochrome P450 enzymes (CYP) is gaining momentum. In this context, the role of N-oxides for in vitro CYP inhibition has not been evaluated. The objectives of this study were: (a) to examine in vitro CYP inhibition of N-oxides of clozapine, levofloxacin, roflumilast, voriconazole and zopiclone in a tiered approach and (b) evaluate in vitro fate of aforementioned N-oxides examined in recombinant CYPs, human microsomes and hepatocytes...
November 16, 2016: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27852962/anatomy-and-immunochemical-characterization-of-the-non-arterial-peptidergic-diffuse-dural-innervation-of-the-rat-and-rhesus-monkey-implications-for-functional-regulation-and-treatment-in-migraine
#14
Frank L Rice, Jennifer Y Xie, Phillip J Albrecht, Emily Acker, Justin Bourgeois, Edita Navratilova, David W Dodick, Frank Porreca
OBJECTIVE: The interplay between neuronal innervation and other cell types underlies the physiological functions of the dura mater and contributes to pathophysiological conditions such as migraine. We characterized the extensive, but understudied, non-arterial diffuse dural innervation (DDI) of the rat and Rhesus monkey. METHODS: We used a comprehensive integrated multi-molecular immunofluorescence labeling strategy to extensively profile the rat DDI and to a lesser extent that of the Rhesus monkey...
November 16, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27843962/a-comparison-of-five-common-drug-drug-interaction-software-programs-regarding-accuracy-and-comprehensiveness
#15
Raziyeh Kheshti, Mohammadsadegh Aalipour, Soha Namazi
OBJECTIVE: Drug-drug interactions (DDIs) can cause failure in treatment and adverse events. DDIs screening software is an important tool to aid clinicians in the detection and management of DDIs. However, clinicians should be aware of the advantages and limitations of these programs. We compared the ability of five common DDI programs to detect clinically important DDIs. METHODS: Lexi-Interact, Micromedex Drug Interactions, iFacts, Medscape, and Epocrates were evaluated...
October 2016: Journal of Research in Pharmacy Practice
https://www.readbyqxmd.com/read/27836670/in-vitro-to-in-vivo-extrapolation-of-the-complex-drug-drug-interaction-of-bupropion-and-its-metabolites-with-cyp2d6-simultaneous-reversible-inhibition-and-cyp2d6-downregulation
#16
Jennifer E Sager, Sasmita Tripathy, Lauren S L Price, Abhinav Nath, Justine Chang, Alyssa Stephenson-Famy, Nina Isoherranen
Bupropion is a widely used antidepressant and smoking cessation aid and a strong inhibitor of CYP2D6 in vivo. Bupropion is administered as a racemic mixture of R- and S-bupropion and has stereoselective pharmacokinetics. Four primary metabolites of bupropion, threo- and erythro-hydrobupropion and R,R- and S,S-OH-bupropion, circulate at higher concentrations than the parent drug and are believed to contribute to the efficacy and side effects of bupropion as well as to the CYP2D6 inhibition. However, bupropion and its metabolites are only weak inhibitors of CYP2D6 in vitro, and the magnitude of the in vivo drug-drug interactions (DDI) caused by bupropion cannot be explained by the in vitro data even when CYP2D6 inhibition by the metabolites is accounted for...
November 9, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27822925/national-rules-for-drug-drug-interactions-are-they-appropriate-for-tertiary-hospitals
#17
Insook Cho, Jae Ho Lee, Jinwook Choi, Hee Hwang, David W Bates
The application of appropriate rules for drug-drug interactions (DDIs) could substantially reduce the number of adverse drug events. However, current implementations of such rules in tertiary hospitals are problematic as physicians are receiving too many alerts, causing high override rates and alert fatigue. We investigated the potential impact of Korean national DDI rules in a drug utilization review program in terms of their severity coverage and the clinical efficiency of how physicians respond to them. Using lists of high-priority DDIs developed with the support of the U...
December 2016: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/27822600/clarithromycin-midazolam-and-digoxin-application-of-pbpk-modeling-to-gain-new-insights-into-drug-drug-interactions-and-co-medication-regimens
#18
Daniel Moj, Nina Hanke, Hannah Britz, Sebastian Frechen, Tobias Kanacher, Thomas Wendl, Walter Emil Haefeli, Thorsten Lehr
Clarithromycin is a substrate and mechanism-based inhibitor of cytochrome P450 (CYP) 3A4 as well as a substrate and competitive inhibitor of P-glycoprotein (P-gp) and organic anion-transporting polypeptides (OATP) 1B1 and 1B3. Administered concomitantly, clarithromycin causes drug-drug interactions (DDI) with the victim drugs midazolam (CYP3A4 substrate) and digoxin (P-gp substrate). The objective of the presented study was to build a physiologically based pharmacokinetic (PBPK) DDI model for clarithromycin, midazolam, and digoxin and to exemplify dosing adjustments under clarithromycin co-treatment...
November 7, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27821711/low-potential-of-basimglurant-to-be-involved-in-drug-drug-interactions-influence-of-non-michaelis-menten-cyp-kinetics-on-fraction-metabolized
#19
Stephen M Fowler, Elena Guerini, NaHong Qiu, Yumi Cleary, Neil J Parrott, Gerard Greig, Navita L Mallalieu
Basimglurant, a novel mGlu5 negative allosteric modulator under development for the treatment of major depressive disorder, is cleared via cytochrome P450 (CYP) mediated oxidative metabolism. Initial enzyme phenotyping studies indicated that CYP3A4/5 dominated basimglurant metabolism and highlighted a risk for drug-drug interactions when comedicated with strong CYP3A4/5 inhibitors or inactivators. However, a clinical drug-drug interaction (DDI) study using the potent and selective CYP3A4/5 inhibitor ketoconazole resulted in an AUCi/AUC ratio of only 1...
November 7, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27821435/what-can-be-learned-from-recent-new-drug-applications-a-systematic-review-of-drug-interaction-data-for-drugs-approved-by-the-u-s-fda-in-2015
#20
Jingjing Yu, Zhu Zhou, Katie H Owens, Tasha K Ritchie, Isabelle Ragueneau-Majlessi
As a follow-up to previous reviews, the aim of the present analysis was to systematically examine all drug metabolism, transport, PK, and DDI data available in the 33 NDAs and 12 BLAs approved by the FDA in 2015, using the University of Washington Drug Interaction Database©, and to highlight the significant findings. All of the NDAs were well-characterized with regard to drug metabolism, transport, and/or organ impairment, and were fully analyzed in this review. In vitro, a majority of the NMEs were found to be substrates or inhibitors/inducers of at least one DME or transporter...
November 7, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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