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https://www.readbyqxmd.com/read/29338933/physiological-based-pharmacokinetic-modeling-to-estimate-in%C3%A2-vivo-ki-of-ketoconazole-on-renal-p-gp-using-human-drug-drug-interaction-study-result-of-fesoterodine-and-ketoconazole
#1
Masayo Oishi, Yuma Takano, Yutaka Torita, Bimal Malhotra, Koji Chiba
This study was conducted to estimate in vivo inhibition constant (Ki) of ketoconazole on renal P-glycoprotein (P-gp) using human drug-drug interaction (DDI) study result of fesoterodine and ketoconazole. Fesoterodine is a prodrug which is extensively hydrolyzed by non-specific esterases to the active metabolite 5-hydroxymethyl tolterodine (5-HMT). 5-HMT is then further metabolized via Cytochrome P450 (CYP) 2D6 and CYP3A4. It is reported that 5-HMT is a substrate of P-gp whereas fesoterodine is not. Renal clearance of 5-HMT is approximately two-times greater than renal glomerular filtration rate...
November 15, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29314617/increased-risk-donors-a-bird-in-the-hand
#2
EDITORIAL
Daniel R Kaul
Unexpected donor-derived infections (DDI) are relatively uncommon events complicating less than 1% of solid organ transplants (1). Disease can be severe, however, with malignancies and agents that infect the central nervous system carrying a particularly high risk of adverse outcomes (2). In most cases, this risk is managed by a combination of clinical assessment and pre-procurement donor testing. This article is protected by copyright. All rights reserved.
January 4, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29304072/potential-drug-drug-interactions-and-their-risk-factors-in-pediatric-patients-admitted-to-the-emergency-department-of-a-tertiary-care-hospital-in-mexico
#3
Olga Morales-Ríos, Luis Jasso-Gutiérrez, Alfonso Reyes-López, Juan Garduño-Espinosa, Onofre Muñoz-Hernández
BACKGROUND: Drug-drug interactions (DDIs) detected in a patient may not be clinically apparent (potential DDIs), and when they occur, they produce adverse drug reactions (ADRs), toxicity or loss of treatment efficacy. In pediatrics, there are only few publications assessing potential DDIs and their risk factors. There are no studies in children admitted to emergency departments (ED). The present study estimates the prevalence and describes the characteristics of potential DDIs in patients admitted to an ED from a tertiary care hospital in Mexico; in addition, potential DDI-associated risk factors are investigated...
2018: PloS One
https://www.readbyqxmd.com/read/29297772/assessment-of-drug-drug-interaction-potential-and-pbpk-modeling-of-cc-223-a-potent-inhibitor-of-the-mammalian-target-of-rapamycin-kinase
#4
Zeen Tong, Rangaraj Narayanan, Christian Atsriku, Jim Nissel, Yan Li, Hong Liu, Xiaomin Wang, Sekhar Surapaneni
1. CC-223 was studied in vitro for metabolism and drug-drug interactions (DDI), and in clinic for interaction with ketoconazole. 2. In vitro, human metabolites of CC-223 included O-desmethyl CC-223 (M1), keto (M2), N-oxide (M3), and imine (M13), with M1 being the most prominent metabolite. 3. CC-223 was metabolized by CYP2C9 and CYP3A, while metabolism of M1 was mediated by CYP2C8 and CYP3A. Ketoconazole increased CC-223 and M1 exposure by 60-70% in healthy volunteers. 4. CC-223 (IC50 ≥ 27 µM) and M1 (IC50 ≥ 46 µM) were inhibitors of CYP2C9 and CYP2C19 in human liver microsomes...
January 3, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29297301/dependency-based-long-short-term-memory-network-for-drug-drug-interaction-extraction
#5
Wei Wang, Xi Yang, Canqun Yang, Xiaowei Guo, Xiang Zhang, Chengkun Wu
BACKGROUND: Drug-drug interaction extraction (DDI) needs assistance from automated methods to address the explosively increasing biomedical texts. In recent years, deep neural network based models have been developed to address such needs and they have made significant progress in relation identification. METHODS: We propose a dependency-based deep neural network model for DDI extraction. By introducing the dependency-based technique to a bi-directional long short term memory network (Bi-LSTM), we build three channels, namely, Linear channel, DFS channel and BFS channel...
December 28, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29278992/comorbidity-polytherapy-and-drug-interactions-in-a-neurological-context-an-example-of-a-multidisciplinary-approach-to-promote-the-rational-use-of-drugs
#6
Giulia Busa, Alessandro Burlina, Vera Damuzzo, Marco Chiumente, Angelo C Palozzo
PURPOSE: A high number of adverse drug reactions (ADRs), mainly caused by drug-drug interactions (DDIs), occur in neurological wards and few data are available about incidence and prevalence of DDIs in this context. This study investigated-(1) the prevalence of drug-drug and drug-disease interactions in patients admitted to a neurological unit in Italy, (2) the risk factors for DDIs, and (3) the diseases and the drug classes mostly involved in drug-drug and drug-disease interactions. METHODS: For 2 months, we performed a retrospective, observational study in the neurological unit of St Bassiano Hospital, enrolling 79 patients who received a drug prescription at discharge...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/29277663/oat1-and-oat3-also-mediate-the-drug-drug-interaction-between-piperacillin-and-tazobactam
#7
Shijie Wen, Changyuan Wang, Yingjie Duan, Xiaokui Huo, Qiang Meng, Zhihao Liu, Shilei Yang, Yanna Zhu, Huijun Sun, Xiaodong Ma, Siyun Yang, Kexin Liu
This study aimed to demonstrate that organic anion transporters (OATs) mediate the drug-drug interaction (DDI) between piperacillin and tazobactam. After co-administration with piperacillin in rats, the AUC of tazobactam in plasma was significantly increased, and t1/2β was prolonged with significant reduction in plasma clearance, renal clearance and cumulative urinary excretion. In rat and human kidney slices, probenecid, p-aminohippurate and benzylpenicillin inhibited the uptake of piperacillin and tazobactam...
December 22, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29247736/metabolic-pathway-of-icotinib-in-vitro-the-differential-roles-of-cyp3a4-cyp3a5-and-cyp1a2-on-potential-pharmacokinetic-drug-drug-interaction
#8
TianHong Zhang, KeRong Zhang, Li Ma, Zheng Li, Juan Wang, YunXia Zhang, Chuang Lu, MingShe Zhu, XiaoMei Zhuang
Icotinib is the self-developed small molecule drug in China for targeted therapy of non-small-cell lung cancer. To date, systematic studies on the pharmacokinetic drug-drug interaction (DDI) of icotinib were limited. By identifying metabolite generation in human liver microsomes (HLM) and revealing the contributions of major CYPs in the formation of major metabolites, the aim of the present work is to understand the mechanisms underlying pharmacokinetic and pharmacological variability in clinic. A LC/UV/HRMS method was developed to characterize the icotinib metabolites...
December 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29246313/assessment-of-the-drug-interaction-potential-of-unconjugated-and-galnac3-conjugated-2-moe-asos
#9
Colby S Shemesh, Rosie Z Yu, Mark S Warren, Michael Liu, Mirza Jahic, Brandon Nichols, Noah Post, Song Lin, Daniel A Norris, Eunju Hurh, Jane Huang, Tanya Watanabe, Scott P Henry, Yanfeng Wang
Antisense oligonucleotides are metabolized by nucleases and drug interactions with small drug molecules at either the cytochrome P450 (CYP) enzyme or transporter levels have not been observed to date. Herein, a comprehensive in vitro assessment of the drug-drug interaction (DDI) potential was carried out with four 2'-O-(2-methoxyethyl)-modified antisense oligonucleotides (2'-MOE-ASOs), including a single triantennary N-acetyl galactosamine (GalNAc3)-conjugated ASO. Several investigations to describe the DDI potential of a 2'-MOE-ASO conjugated to a high-affinity ligand for hepatocyte-specific asialoglycoprotein receptors are explored...
December 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29245320/qtc-prolongation-and-torsades-de-pointes-due-to-a-coadministration-of-fluoxetine-and-amiodarone-in-a-patient-with-implantable-cardioverter-defibrillator-case-report-and-review-of-the-literature
#10
Anhua Wei, Jinlan Peng, Zhichun Gu, Juan Li
RATIONALE: Drug-induced prolongation of the corrected QT interval (QTc) may lead to serious and potentially life-threatening ventricular tachyarrhythmia, such as torsades de pointes (Tdp), which is worthy of clinical attention. Here, we report 1 case of Tdp after a coadministration of fluoxetine and amiodarone. PATIENT CONCERNS: A 62-year-old Chinese male who placed with the implanted cardioverter-defibrillator (ICD) appeared the QTc prolongation and Tdp after the concurrent administration of fluoxetine and amiodarone...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29243231/gaining-mechanistic-insight-into-coproporphyrin-i-as-endogenous-biomarker-for-oatp1b-mediated-drug-drug-interactions-using-population-pharmacokinetic-modelling-and-simulation
#11
Shelby Barnett, Kayode Ogungbenro, Karelle Ménochet, Hong Shen, Yurong Lai, W Griffith Humphreys, Aleksandra Galetin
This study evaluates coproporphyrin I (CPI) as a selective endogenous biomarker of OATP1B-mediated drug-drug interactions (DDIs) relative to clinical probe rosuvastatin using nonlinear mixed-effect modelling. Plasma and urine CPI data in the presence/absence of rifampicin were modelled to describe CPI synthesis, elimination clearances and obtain rifampicin in vivo OATP Ki. The biomarker showed stable inter-occasion baseline concentrations and low inter-individual variability (<25%) in subjects with wild type SLCO1B1...
December 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29241088/development-of-an-lc-ms-method-to-quantify-coproporphyrin-i-and-iii-as-endogenous-biomarkers-for-drug-transporter-mediated-drug-drug-interactions
#12
Emmanuel Njumbe Ediage, Lieve Dillen, Ann Vroman, Luc Diels, Annett Kunze, Jan Snoeys, Tom Verhaeghe
Coproporphyrins are proposed as endogenous biomarkers of hepatic Organic Anion Transporting Polypeptide (OATP)1B functional activity. In this study, a new sample extraction method based on a mixed-mode anion exchange sorbent (SPE clean-up using Oasis 30mg Max 96 well plates) was developed for absolute quantification of coproporphyrin I and III (CP-I and CP-III) in human plasma. Chromatographic separation was performed with an Ace Excel 2 C18 PFP, 3μm, 2.1×150mm, maintained at 60°C. A 10mM ammonium formate containing 0...
December 6, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29231225/unusual-phonon-behavior-and-ultra-low-thermal-conductance-of-monolayer-inse
#13
Hangbo Zhou, Yongqing Cai, Gang Zhang, Yong-Wei Zhang
Monolayer indium selenide (InSe) possesses numerous fascinating properties, such as high electron mobility, quantum Hall effect and anomalous optical response. However, its phonon properties, thermal transport properties and the origin of its structural stability remain unexplored. Using first-principles calculations, we show that the atoms in InSe are highly polarized and such polarization causes strong long-range dipole-dipole interaction (DDI). For acoustic modes, DDI is essential for maintaining its structural stability...
December 12, 2017: Nanoscale
https://www.readbyqxmd.com/read/29226313/model-based-assessments-of-cyp-mediated-drug-drug-interaction-risk-of-alectinib-physiologically-based-pharmacokinetic-modeling-supported-clinical-development
#14
Yumi Cleary, Michael Gertz, Peter N Morcos, Li Yu, Kuresh Youdim, Alex Phipps, Stephen Fowler, Neil Parrott
Alectinib is a selective anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive non-small cell lung cancer. Alectinib and its major active metabolite M4 exhibited drug-drug interaction (DDI) potential through cytochrome P450 (CYP) enzymes CYP3A4 and CYP2C8 in vitro. Clinical relevance of the DDI risk was investigated as part of a rapid development program to fulfil the breakthrough therapy designation. Therefore, a strategy with a combination of physiologically based pharmacokinetic (PBPK) modeling and limited clinical trials focused on generating informative data for modeling was taken to ensure extrapolation ability of DDI risk...
December 11, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29225780/the-decision-to-delivery-interval-in-emergency-caesarean-sections-impact-of-anaesthetic-technique-and-work-shift
#15
Anette Hein, David Thalen, Ylva Eriksson, Jan G Jakobsson
Background: One important task of the emergency anaesthesia service is to provide rapid, safe and effective anaesthesia for emergency caesarean sections (ECS). A Decision to Delivery Interval (DDI) <30 minutes for ECS is a quality indicator for this service. The aim of this study was to assess the DDI and the impact of chosen anaesthetic technique (general anaesthesia (GA), spinal anaesthesia (SPA) with opioid supplementation, or "top-up" of labour epidural analgesia (tEDA) with local anaesthesia and fentanyl mixture) and work shift for ECS at Danderyds Hospital, Sweden...
2017: F1000Research
https://www.readbyqxmd.com/read/29219066/a-multi-network-clustering-method-for-detecting-protein-complexes-from-multiple-heterogeneous-networks
#16
Le Ou-Yang, Hong Yan, Xiao-Fei Zhang
BACKGROUND: The accurate identification of protein complexes is important for the understanding of cellular organization. Up to now, computational methods for protein complex detection are mostly focus on mining clusters from protein-protein interaction (PPI) networks. However, PPI data collected by high-throughput experimental techniques are known to be quite noisy. It is hard to achieve reliable prediction results by simply applying computational methods on PPI data. Behind protein interactions, there are protein domains that interact with each other...
December 1, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29212457/the-decision-delivery-interval-in-emergency-caesarean-section-and-its-associated-maternal-and-fetal-outcomes-at-a-referral-hospital-in-northern-tanzania-a-cross-sectional-study
#17
Birjna A Hirani, Bariki L Mchome, Nicholaus S Mazuguni, Michael J Mahande
BACKGROUND: Decision delivery interval (DDI) is the time line between a decision to conduct an emergency caesarean section and actual delivery of the baby. Prolong DDI constitute a third phase delay in provision of emergency obstetric care. Intervention designed to minimize DDI are vital, in attempt to prevent maternal morbidity and neonatal morbidity and mortality. The feasibility and practicability of the recommended DDI in recent studies have been questioned especially in limited resource setting and therefore the objective of our study was to determine the DDI and its associated fetalmaternal outcomes at a tertiary referral hospital in Tanzania...
December 7, 2017: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/29204687/a-physiologically-based-pharmacokinetic-pbpk-parent-metabolite-model-of-the-chemotherapeutic-zoptarelin-doxorubicin-integration-of-in-vitro-results-phase-i-and-phase-ii-data-and-model-application-for-drug-drug-interaction-potential-analysis
#18
Nina Hanke, Michael Teifel, Daniel Moj, Jan-Georg Wojtyniak, Hannah Britz, Babette Aicher, Herbert Sindermann, Nicola Ammer, Thorsten Lehr
PURPOSE: Zoptarelin doxorubicin is a fusion molecule of the chemotherapeutic doxorubicin and a luteinizing hormone-releasing hormone receptor (LHRHR) agonist, designed for drug targeting to LHRHR positive tumors. The aim of this study was to establish a physiologically based pharmacokinetic (PBPK) parent-metabolite model of zoptarelin doxorubicin and to apply it for drug-drug interaction (DDI) potential analysis. METHODS: The PBPK model was built in a two-step procedure...
December 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29203651/development-and-validation-of-a-high-throughput-transcriptomic-biomarker-to-address-21st-century-genetic-toxicology-needs
#19
Heng-Hong Li, Renxiang Chen, Daniel R Hyduke, Andrew Williams, Roland Frötschl, Heidrun Ellinger-Ziegelbauer, Raegan O'Lone, Carole L Yauk, Jiri Aubrecht, Albert J Fornace
Interpretation of positive genotoxicity findings using the current in vitro testing battery is a major challenge to industry and regulatory agencies. These tests, especially mammalian cell assays, have high sensitivity but suffer from low specificity, leading to high rates of irrelevant positive findings (i.e., positive results in vitro that are not relevant to human cancer hazard). We developed an in vitro transcriptomic biomarker-based approach that provides biological relevance to positive genotoxicity assay data, particularly for in vitro chromosome damage assays, and propose its application for assessing the relevance of the in vitro positive results to carcinogenic hazard...
December 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29202203/user-needs-analysis-and-usability-assessment-of-datamed-a-biomedical-data-discovery-index
#20
Ram Dixit, Deevakar Rogith, Vidya Narayana, Mandana Salimi, Anupama Gururaj, Lucila Ohno-Machado, Hua Xu, Todd R Johnson
Objective: To present user needs and usability evaluations of DataMed, a Data Discovery Index (DDI) that allows searching for biomedical data from multiple sources. Materials and Methods: We conducted 2 phases of user studies. Phase 1 was a user needs analysis conducted before the development of DataMed, consisting of interviews with researchers. Phase 2 involved iterative usability evaluations of DataMed prototypes. We analyzed data qualitatively to document researchers' information and user interface needs...
November 30, 2017: Journal of the American Medical Informatics Association: JAMIA
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