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https://www.readbyqxmd.com/read/28339701/comparison-of-three-commercial-knowledge-bases-for-detection-of-drug-drug-interactions-in-clinical-decision-support
#1
Kin Wah Fung, Joan Kapusnik-Uner, Jean Cunningham, Stefanie Higby-Baker, Olivier Bodenreider
Objective: : To compare 3 commercial knowledge bases (KBs) used for detection and avoidance of potential drug-drug interactions (DDIs) in clinical practice. Methods: : Drugs in the DDI tables from First DataBank (FDB), Micromedex, and Multum were mapped to RxNorm. The KBs were compared at the clinical drug, ingredient, and DDI rule levels. The KBs were evaluated against a reference list of highly significant DDIs from the Office of the National Coordinator for Health Information Technology (ONC)...
February 22, 2017: Journal of the American Medical Informatics Association: JAMIA
https://www.readbyqxmd.com/read/28334018/development-of-an-evidence-evaluation-and-synthesis-system-for-drug-drug-interactions-and-its-application-to-a-systematic-review-of-hiv-and-malaria-co-infection
#2
Kay Seden, Sara Gibbons, Catia Marzolini, Jonathan M Schapiro, David M Burger, David J Back, Saye H Khoo
BACKGROUND: In all settings, there are challenges associated with safely treating patients with multimorbidity and polypharmacy. The need to characterise, understand and limit harms resulting from medication use is therefore increasingly important. Drug-drug interactions (DDIs) are prevalent in patients taking antiretrovirals (ARVs) and if unmanaged, may pose considerable risk to treatment outcome. One of the biggest challenges in preventing DDIs is the substantial gap between theory and clinical practice...
2017: PloS One
https://www.readbyqxmd.com/read/28320730/prediction-of-the-transporter-mediated-drug-drug-interaction-potential-of-dabrafenib-and-its-major-circulating-metabolites
#3
Harma Ellens, Marta Johnson, Sarah K Lawrence, Cory A Watson, Liangfu Chen, Lauren E Richards-Peterson
The BRAF inhibitor dabrafenib was recently approved for the treatment of certain BRAF V600 mutation-positive tumors, either alone or in combination therapy with the MEK inhibitor trametinib. This article presents the dabrafenib transporter-mediated drug-drug interaction risk assessment, which is currently an important part of drug development, regulatory submission and drug registration. Dabrafenib and its major circulating metabolites (hydroxy-, carboxy- and desmethyl-dabrafenib) were investigated as inhibitors of the clinically relevant transporters Pgp, BCRP, OATP1B1, OATP1B3, OCT2, OAT1 and OAT3...
March 20, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28316654/predicting-drug-drug-interactions-through-drug-structural-similarities-and-interaction-networks-incorporating-pharmacokinetics-and-pharmacodynamics-knowledge
#4
Takako Takeda, Ming Hao, Tiejun Cheng, Stephen H Bryant, Yanli Wang
Drug-drug interactions (DDIs) may lead to adverse effects and potentially result in drug withdrawal from the market. Predicting DDIs during drug development would help reduce development costs and time by rigorous evaluation of drug candidates. The primary mechanisms of DDIs are based on pharmacokinetics (PK) and pharmacodynamics (PD). This study examines the effects of 2D structural similarities of drugs on DDI prediction through interaction networks including both PD and PK knowledge. Our assumption was that a query drug (Dq) and a drug to be examined (De) likely have DDI if the drugs in the interaction network of De are structurally similar to Dq...
2017: Journal of Cheminformatics
https://www.readbyqxmd.com/read/28299402/comparative-analysis-of-three-drug-drug-interaction-screening-systems-against-probable-clinically-relevant-drug-drug-interactions-a-prospective-cohort-study
#5
Neža Muhič, Ales Mrhar, Miran Brvar
PURPOSE: Drug-drug interaction (DDI) screening systems report potential DDIs. This study aimed to find the prevalence of probable DDI-related adverse drug reactions (ADRs) and compare the clinical usefulness of different DDI screening systems to prevent or warn against these ADRs. METHODS: A prospective cohort study was conducted in patients urgently admitted to medical departments. Potential DDIs were checked using Complete Drug Interaction®, Lexicomp® Online™, and Drug Interaction Checker®...
March 15, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28296193/investigating-transporter-mediated-drug-drug-interactions-using-a-physiologically-based-pharmacokinetic-model-of-rosuvastatin
#6
Q Wang, M Zheng, T Leil
Rosuvastatin is a frequently used probe in transporter-mediated drug-drug interaction (DDI) studies. This report describes the development of a physiologically based pharmacokinetic (PBPK) model of rosuvastatin for prediction of pharmacokinetic (PK) DDIs. The rosuvastatin model predicted the observed single (i.v. and oral) and multiple dose PK profiles, as well as the impact of coadministration with transporter inhibitors. The predicted effects of rifampin and cyclosporine (6.58-fold and 5.07-fold increase in rosuvastatin area under the curve (AUC), respectively) were mediated primarily via inhibition of hepatic organic anion-transporting polypeptide (OATP)1B1 (Inhibition constant (Ki ) ∼1...
March 13, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28289057/applying-stable-isotope-labeled-amino-acids-in-micropatterned-hepatocyte-co-culture-to-directly-determine-the-degradation-rate-constant-for-cyp3a4
#7
Ryan H Takahashi, Sheerin Shahidi-Latham, Susan Wong, Jae H Chang
The rate of enzyme degradation (kdeg) is an important input parameter for the prediction of clinical drug-drug-interactions (DDI) that result from mechanism-based inactivation or induction of cytochrome P450s. Currently, a large range of reported estimates for CYP3A4 enzyme degradation exists, and consequently, large uncertainty exists in steady-state predictions for DDI. In the current investigations, stable isotope labeled amino acids in culture (SILAC) was applied to a long-lived primary human hepatocyte culture, HepatoPac, to directly monitor the degradation of CYP3A4...
March 13, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28285369/diclofenac-sex-divergent-drug-drug-interaction-with-sunitinib-pharmacokinetics-and-tissue-distribution-in-male-and-female-mice
#8
Chii Chii Chew, Salby Ng, Yun Lee Chee, Teng Wai Koo, Ming Hui Liew, Evelyn Li-Ching Chee, Pilar Modamio, Cecilia Fernández, Eduardo L Mariño, Ignacio Segarra
Coadministration of diclofenac and sunitinib, tyrosine kinase inhibitor, led to sex-divergent pharmacokinetic drug-drug interaction outcomes. Male and female mice were administered 60 mg/kg PO sunitinib alone (control groups) or with 30 mg/kg PO diclofenac. Sunitinib concentration in plasma, brain, kidney and liver were determined by HPLC and non-compartmental pharmacokinetic parameters calculated. In male mice, diclofenac decreased AUC0→∞ 38% in plasma (p < 0.05) and 24% in liver (p < 0.001) and 23% in kidney (p < 0...
March 11, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28281257/dna-directed-antibody-immobilization-for-robust-protein-microarrays-application-to-single-particle-detection-dna-directed-antibody-immobilization
#9
Nese Lortlar Ünlü, Fulya Ekiz Kanik, Elif Seymour, John H Connor, M Selim Ünlü
Protein microarrays are emerging tools which have become very powerful in multiplexed detection technologies. A variety of proteins can be immobilized on a sensor chip allowing for multiplexed diagnostics. Therefore, various types of analyte in a small volume of sample can be detected simultaneously. Protein immobilization is a crucial step for creating a robust and sensitive protein microarray-based detection system. In order to achieve a successful protein immobilization and preserve the activity of the proteins after immobilization, DNA-directed immobilization is a promising technique...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28269534/addressing-drug-drug-and-drug-food-interactions-through-personalized-empowerment-services-for-healthcare
#10
Marios Spanakis, Emmanouil G Spanakis, Haridimos Kondylakis, Stelios Sfakianakis, Irini Genitsaridi, Vangelis Sakkalis, Manolis Tsiknakis, Kostas Marias
Personalized healthcare systems support the provision of timely and appropriate information regarding healthcare options and treatment alternatives. Especially for patients that receive multi-drug treatments a key issue is the minimization of the risk of adverse effects due to drug-drug interactions (DDIs). DDIs may be the result of doctor prescribed drugs but also due to self-medication of conventional drugs, alternative medicines, food habits, alcohol or smoking. It is therefore crucial for personalized health systems, apart from assisting physicians for optimal prescription practices, to also provide appropriate information for individual users for drug-drug interactions or similar information regarding risks for modulation of the ensuing treatment...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28263911/substrate-and-method-dependent-inhibition-of-three-abc-transporters-mdr1-bcrp-and-mrp2
#11
Jenny M Pedersen, Elin K Khan, Christel A S Bergstrom, Johan Palm, Janet Hoogstraate, Per Artursson
Drug transport and drug-drug interactions (DDI) with human ABC transporters are generally investigated in mammalian cell lines or inverted membrane vesicles from insect cells (Sf9) overexpressing the transporter of interest. In this study, we instead used membrane vesicles from human embryonic kidney cells (HEK293) overexpressing wild type MDR1/Pgp (ABCB1), BCRP (ABCG2), and MRP2 (ABCC2) with the aim to study the concentration dependent inhibition of shared and prototypic probe substrates. We first investigated 15 substrates and identified estrone-17-beta-glucorinide (E17G) as shared substrate...
March 2, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28263457/ombitasvir-paritaprevir-ritonavir-and-dasabuvir-drug-interactions-with-antiretroviral-agents-and-drugs-forsubstance-abuse
#12
Jennifer R King, Rajeev M Menon
AbbVie's 3 direct-acting antiviral (3D) regimen containing ombitasvir, paritaprevir, ritonavir, and dasabuvir with and without ribavirin is approved for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection. Safe and efficacious antiviral regimens resulting in minimal to no drug-drug interactions (DDIs) with antiretrovirals are needed to ensure that patients coinfected with HCV and the human immunodeficiency virus (HIV) achieve 12-week sustained virologic response rates similar to HCV-monoinfected patients...
March 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28261547/progress-in-prediction-and-interpretation-of-clinically-relevant-metabolic-drug-drug-interactions-a-minireview-illustrating-recent-developments-and-current-opportunities
#13
REVIEW
Stephen Fowler, Peter N Morcos, Yumi Cleary, Meret Martin-Facklam, Neil Parrott, Michael Gertz, Li Yu
PURPOSE OF REVIEW: This review gives a perspective on the current "state of the art" in metabolic drug-drug interaction (DDI) prediction. We highlight areas of successful prediction and illustrate progress in areas where limits in scientific knowledge or technologies prevent us from having full confidence. RECENT FINDINGS: Several examples of success are highlighted. Work done for bitopertin shows how in vitro and clinical data can be integrated to give a model-based understanding of pharmacokinetics and drug interactions...
2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28260951/the-effect-of-apixaban-on-the-pharmacokinetics-of-digoxin-and-atenolol-in-healthy-subjects
#14
Charles Frost, Yan Song, Zhigang Yu, Jessie Wang, Lois S Lee, Alan Schuster, Allyson Pollack, Frank LaCreta
PURPOSE: Apixaban is often coadministered with treatments for cardiovascular comorbidities, which may lead to unintended drug-drug interactions (DDIs). The effects of apixaban on pharmacokinetics (PK) of multidose Lanoxin(®) (digoxin) and single-dose Tenormin(®) (atenolol) and the effects of single-dose atenolol on apixaban PK in healthy subjects were investigated in two Phase 1 studies. PATIENTS AND METHODS: The digoxin DDI study was an open-label, multidose, two-treatment, single-sequence study in which subjects received digoxin 0...
2017: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/28258068/novel-method-to-predict-in-vivo-liver-to-plasma-kpuu-for-oatp-substrates-using-suspension-hepatocytes
#15
Keith Riccardi, Jian Lin, Zhenhong Li, Mark Niosi, Sangwoo Ryu, Wenyi Hua, Karen Atkinson, Rachel E Kosa, John Litchfield, Li Di
The ability to predict human liver-to-plasma unbound partition coefficient (Kpuu) is of great importance to estimate unbound liver concentration, develop PK/PD relationships, predict efficacy and toxicity in the liver, and model drug-drug interaction (DDI) potential for drugs that are asymmetrically distributed into the liver. A novel in vitro method has been developed to predict in vivo Kpuu with good accuracy using cryopreserved suspension hepatocytes in InVitroGRO HI media with 4% BSA. Validation was performed using six OATP substrates with rat in vivo Kpuu data from IV infusion studies where steady state was achieved...
March 3, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28254952/effects-of-microrna-34a-on-the-pharmacokinetics-of-cytochrome-p450-probe-drugs-in-mice
#16
Joseph L Jilek, Ye Tian, Ai-Ming Yu
MicroRNAs (miR) including miR-34a have been shown to regulate nuclear receptor, drug-metabolizing enzyme and transporter gene expression in various cell model systems. However, to what degree miRNAs would affect pharmacokinetics (PK) at the systemic level remains unknown. Additionally, miR-34a replacement therapy represents a new cancer treatment strategy, whereas it is undefined if miR-34a therapeutics would causes any drug-drug interactions (DDI). To address the questions, we developed a practical single-mouse PK approach and investigated the effects of a bioengineered miR-34a agent on the PK of multiple Cytochrome P450 (CYP) probe drugs (midazolam, dextromethorphan, phenacetin, diclofenac, and chlorzoxazone) administered as a cocktail to mouse models...
March 2, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28254951/examination-of-the-human-cytochrome-p4503a4-induction-potential-of-pf-06282999-an-irreversible-myeloperoxidase-inactivator-integration-of-preclinical-in-silico-and-biomarker-methodologies-in-the-prediction-of-the-clinical-outcome
#17
Jennifer Dong, James Gosset, Odette Fahmi, Zhiwu Lin, Jeffrey Chabot, Steven Terra, Vu Le, Kristin Chidsey, Parya Nouri, Albert Kim, Leonard Buckbinder, Amit S Kalgutkar
The propensity for cytochrome P450 (CYP)3A4 induction by 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999), an irreversible inactivator of myeloperoxidase, was examined in the present work. Studies using human hepatocytes revealed moderate increases in CYP3A4 messenger RNA (mRNA) and midazolam-1'-hydroxylase activity in a PF-06282999 dose-dependent fashion. At the highest tested concentration of 300 μM, PF-06282999 caused maximal induction in CYP3A4 mRNA and enzyme activity ranging from 56% - 86% and 47% - 72%, respectively, of rifampicin response across the three hepatocyte donor pools...
March 2, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28249913/alteration-of-hemostatic-parameters-in-patients-with-different-levels-of-subclinical-hypothyroidism-and-the-effect-of-l-thyroxine-treatment
#18
Fang Gao, Guangya Wang, Jinxiu Xu
Subclinical hypothyroidism (SH) is associated with hypercoagulability and hypofibrinolysis. The objective of this study was to assess the effect of L-thyroxine (L-T4) treatment and to evaluate changes in the hemostatic abnormalities of patients with varying severities of SH. We measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer (DDI), fibrinogen (FIB), platelet counts (PLT), mean platelet volume (MPV), platelet distribution width (PDW), activated partial thromboplastin time (APTT), and prothrombin time (PT) in 149 female subjects...
January 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28249566/positive-unlabeled-learning-for-inferring-drug-interactions-based-on-heterogeneous-attributes
#19
Pathima Nusrath Hameed, Karin Verspoor, Snezana Kusljic, Saman Halgamuge
BACKGROUND: Investigating and understanding drug-drug interactions (DDIs) is important in improving the effectiveness of clinical care. DDIs can occur when two or more drugs are administered together. Experimentally based DDI detection methods require a large cost and time. Hence, there is a great interest in developing efficient and useful computational methods for inferring potential DDIs. Standard binary classifiers require both positives and negatives for training. In a DDI context, drug pairs that are known to interact can serve as positives for predictive methods...
March 1, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28246687/-multimorbidity-management-and-the-physician-s-daily-clinical-dilemma
#20
E Battegay, M Cheetham, B M Holzer, A Nowak, D Schmidt, S Rampini
About 20-25% of all persons and about 90% of all patients who are acutely hospitalized in internal medicine departments have multiple acute or chronic diseases. They are multimorbid. The encounter with multimorbid patients has become the most common situation in the health care system. Theoretically, multimorbidity results in an innumerable potential disease constellations. In addition, the likelihood of interactions between diseases (disease-disease interactions, DDI) and the complexity increases overproportionately with each additional disease...
February 28, 2017: Der Internist
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