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https://www.readbyqxmd.com/read/29786959/assessment-of-the-drug-interaction-potential-of-ertugliflozin-with-sitagliptin-metformin-glimepiride-or-simvastatin-in-healthy-subjects
#1
Vikas Kumar Dawra, David L Cutler, Susan Zhou, Rajesh Krishna, Haihong Shi, Yali Liang, Christine Alvey, Anne Hickman, Didier Saur, Steven G Terra, Vaishali Sahasrabudhe
Ertugliflozin, a sodium-glucose cotransporter 2 inhibitor for the treatment of adults with type 2 diabetes mellitus, is expected to be coadministered with sitagliptin, metformin, glimepiride, and/or simvastatin. Four separate open-label, randomized, single-dose, crossover studies were conducted in healthy adults to assess the potential pharmacokinetic interactions between ertugliflozin 15 mg and sitagliptin 100 mg (n = 12), metformin 1000 mg (n = 18), glimepiride 1 mg (n = 18), or simvastatin 40 mg (n = 18)...
May 22, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29786857/effect-of-oatp1b1-1b3-inhibitor-gdc-0810-on-the-pharmacokinetics-of-pravastatin-and-coproporphyrin-i-iii-in-healthy-female-subjects
#2
Lichuan Liu, Sravanthi Cheeti, Kenta Yoshida, Edna Choo, Eugene Chen, Buyun Chen, Mary Gates, Stina Singel, Roland Morley, Joseph Ware, Srikumar Sahasranaman
Developed as an oral anticancer drug to treat estrogen receptor-positive breast cancer, GDC-0810 was shown to be a potent inhibitor of organic anion-transporting polypeptide 1B1 and 1B3 (OATP1B1/1B3) from an in vitro assay. A clinical study was conducted to assess the drug-drug interaction potential between GDC-0810 and pravastatin, which is a relatively selective and sensitive OATP1B1/1B3 substrate. Fifteen healthy female subjects of non-childbearing potential were enrolled in the study. On day 1 in period 1, a single 10-mg dose of pravastatin was administered to all subjects...
May 22, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29786810/-epilepsy-and-comorbid-neurodevelopmental-disorders
#3
Viviann Nordin, Ingrid B Olsson, Torbjörn Tomson
In children and adults with epilepsy, it is important to be aware of and diagnose common comorbidities that may have a large impact on quality of life. Comorbid neurodevelopmental disorders include intellectual disability, autism, and attention deficit hyperactivity disorder (ADHD). Depression and anxiety are common findings, and also the risk of psychosis is increased. The medication used to treat these comorbidities is found to be effective with little risks of seizure exacerbation, i.e. medication with methylphenidate, selective serotonin reuptake inhibitors (SSRIs) and second generation neuroleptics...
May 22, 2018: Läkartidningen
https://www.readbyqxmd.com/read/29786712/cocrystals-of-a-1-2-4-thiadiazole-based-potent-neuroprotector-with-gallic-acid-solubility-thermodynamic-stability-relationships-and-formation-pathways
#4
Artem O Surov, Andrei V Churakov, Alexey N Proshin, Xia-Lin Dai, Tongbu Lu, German L Perlovich
Three distinct solid forms, namely anhydrous cocrystals with 2 : 1 and 1 : 1 drug/acid ratios ([TDZ : GA] (2 : 1), [TDZ : GA] (1 : 1)), and a hydrated one having 1 : 1 : 1 drug/acid/water stoichiometry ([TDZ : GA : H2O] (1 : 1 : 1)), have been formed by cocrystallization of the biologically active 1,2,4-thiadiazole derivative (TDZ) with gallic acid (GA). The thermodynamic stability relationships between the cocrystals were rationalized in terms of Gibbs energies of the formation reactions and further verified by performing a set of competitive and exchange mechanochemical reactions...
May 22, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29786605/hydrophobic-interaction-mediated-coating-of-pluronics-on-mesoporous-silica-nanoparticle-with-stimuli-responsiveness-for-cancer-therapy
#5
Luping Sha, Da Wang, Yuling Mao, Wei Shi, Tianbin Gao, Qinfu Zhao, Si-Ling Wang
In this research, a novel method was used to successfully make Pluronic P123 stably coated on mesoporous silica nanoparticles (MSN). That P123 and MSN co-constructed a drug delivery system (DDS) had not been reported. In this DDS, the coating of P123 was realized through hydrophobic interaction with octadecyl chain modified MSN. Experiments found only Pluronic with an appropriate ratio of hydrophilic and lipophilic segment could keep the nanoassemblies stable.
 For comparison, nanoassemblies consisted of P123 and octadecyl chain modified MSN with or without disulfide bond were prepared, which were denoted as PSMSN and PMSN respectively...
May 22, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29786590/hepatitis-c-and-human-rights-comparison-of-legal-experience-of-ukraine-and-georgia
#6
Iryna Y Senyuta
A comparative legal research of human rights provision in Ukraine and Georgia, in the aspect of combating viral HCV, was conducted. Ukrainian advocacy experience and Georgian strategic litigation experience with regard to human rights and HCV was analyzed. Key international instruments, which lay the conceptual foundations as well as outline the measures, which are directed at human rights in patient care provision and fighting viral hepatitis, were elucidated. Attention was paid to the Global health sector strategy...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29786422/mechanisms-regulating-the-association-of-protein-phosphatase-1-with-spinophilin-and-neurabin
#7
Michael C Edler, Asma B Salek, Darryl S Watkins, Harjot Kaur, Cameron W Morris, Bryan K Yamamoto, Anthony J Baucum
Protein phosphorylation is a key mediator of signal transduction, allowing for dynamic regulation of substrate activity. Whereas protein kinases obtain substrate specificity by targeting specific amino acid sequences, serine/threonine phosphatase catalytic subunits are much more promiscuous in their ability to dephosphorylate substrates. To obtain substrate specificity, serine/threonine phosphatases utilize targeting proteins to regulate phosphatase subcellular localization and catalytic activity. Spinophilin and its homolog neurabin are two of the most abundant dendritic spine-localized protein phosphatase 1 (PP1) targeting proteins...
May 22, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29785704/the-role-of-adolescent-victimization-in-energy-drink-consumption-monitoring-the-future-2010-2016
#8
Dylan B Jackson, Wanda E Leal, Chad Posick, Michael G Vaughn, Myrah Olivan
Energy drinks have been linked to a number of deleterious health outcomes among youth. Even so, the underlying risk factors for energy drink consumption among youth are less frequently examined. The present study examines the link between adolescent victimization experiences (i.e., property and violent victimization) and energy drink consumption among a nationally representative sample of adolescents. We employed the seven most recent cohorts (2010-2016) from the Monitoring the Future (MTF) study. A multi-stage random sampling technique was used to acquire the U...
May 21, 2018: Journal of Community Health
https://www.readbyqxmd.com/read/29785610/evaluation-of-strategies-for-the-assessment-of-drug-drug-interactions-involving-cytochrome-p450-enzymes
#9
Jelle Reinen, Martijn Smit, Mira Wenker
BACKGROUND AND OBJECTIVES: Drug-drug interactions (DDIs) can occur when one drug alters the metabolism of another drug. Drug metabolism mediated by cytochrome P450 enzymes (CYPs) is responsible for the majority of metabolism of known drugs and inhibition of CYP enzymes is a well-known cause of DDIs. In the current study, the use of various human liver microsomes (HLM)-based methods to determine occurrence of CYP-mediated metabolism-dependent inhibition (MDI) and possible follow-up studies were evaluated...
May 21, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29785580/a-comprehensive-review-and-meta-analysis-of-risk-factors-for-statin-induced-myopathy
#10
REVIEW
Khoa A Nguyen, Lang Li, Deshun Lu, Aida Yazdanparast, Lei Wang, Rolf P Kreutz, Elizabeth C Whipple, Titus K Schleyer
PURPOSE: To aid prescribers in assessing a patient's risk for statin-induced myopathy (SIM), we performed a comprehensive review of currently known risk factors and calculated aggregated odds ratios for each risk factor through a meta-analysis. METHODS: This meta-analysis was done through four phases: (1) Identification of the relevant primary literature; (2) abstract screening using inclusion and exclusion criteria; (3) detailed review and data extraction; and (4) synthesis and statistical analysis...
May 22, 2018: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29785561/reptb-a-gene-ontology-based-drug-repurposing-approach-for-tuberculosis
#11
Anurag Passi, Neeraj Kumar Rajput, David J Wild, Anshu Bhardwaj
Tuberculosis (TB) is the world's leading infectious killer with 1.8 million deaths in 2015 as reported by WHO. It is therefore imperative that alternate routes of identification of novel anti-TB compounds are explored given the time and costs involved in new drug discovery process. Towards this, we have developed RepTB. This is a unique drug repurposing approach for TB that uses molecular function correlations among known drug-target pairs to predict novel drug-target interactions. In this study, we have created a Gene Ontology based network containing 26,404 edges, 6630 drug and 4083 target nodes...
May 21, 2018: Journal of Cheminformatics
https://www.readbyqxmd.com/read/29785554/interactions-between-kappa-and-mu-opioid-receptor-agonists-effects-of-the-ratio-of-drugs-in-mixtures
#12
Vanessa Minervini, Hannah Y Lu, Jahnavi Padarti, Daniela C Osteicoechea, Charles P France
RATIONALE: Pain is the leading reason for seeking health care, and mu opioid receptor agonists continue to be prescribed despite well-documented adverse effects. Kappa opioid receptor agonists have antinociceptive effects with little to no abuse liability and might be useful for treating pain in mixtures. Kappa:mu opioid mixtures might be useful if therapeutic effects of each drug can be selectively increased while reducing or avoiding the adverse effects that occur with larger doses of each drug alone...
May 22, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29785481/encapsulation-of-theophylline-in-gelatin-a-pectin-complex-coacervates
#13
Nirmala Devi, Chayanika Deka, Prajnya Nath, Dilip Kumar Kakati
The present study aims at synthesizing gelatin A-pectin complex coacervates and encapsulation of theophylline in the polymer system. Variation and optimization of different reaction parameters such as pH, ratio between the polymers and cross-linker concentration was carried out to attain higher product yield. Relative viscosity, turbidity and UV-visible measurements were done for optimization. The optimum ratio between gelatin A-pectin was fixed at weight ratio 42:8 and pH=3.5. It was further observed that adhesion between the microcapsules decreased by the use of sodium carboxymethyl cellulose (SCMC) to the coacervate...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29785435/assessing-the-performance-of-mm-pbsa-and-mm-gbsa-methods-7-entropy-effects-on-the-performance-of-end-point-binding-free-energy-calculation-approaches
#14
Huiyong Sun, Lili Duan, Fu Chen, Hui Liu, Zhe Wang, Peichen Pan, Feng Zhu, John Z H Zhang, Tingjun Hou
Entropy effects play an important role in drug-target interactions, but the entropic contribution to ligand-binding affinity is often neglected by end-point binding free energy calculation methods, such as MM/GBSA and MM/PBSA, due to the expensive computational cost of normal mode analysis (NMA). Here, we systematically investigated entropy effects on the prediction power of MM/GBSA and MM/PBSA using >1500 protein-ligand systems and six representative AMBER force fields. Two computationally efficient methods, including NMA based on truncated structures and the interaction entropy approach, were used to estimate the entropic contributions to ligand-target binding free energies...
May 22, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29785276/food-intake-attenuates-the-drug-interaction-between-new-quinolones-and-aluminum
#15
Ayuko Imaoka, Kosuke Abiru, Takeshi Akiyoshi, Hisakazu Ohtani
Background: Intestinal absorption of new quinolones is decreased by oral administration of polyvalent metal cations. Some clinical studies have demonstrated this drug - drug interaction is more prominent under fasted condition. However, the effect of food intake on the extent of drug - drug interaction between new quinolones and metal cations remains to be investigated quantitatively and systematically. The aim of this study was to develop an animal model that enables to evaluate the effect of food intake on the extent of drug - drug interaction in the gastrointestinal tract by chelation and to apply the model to evaluate quantitatively the effect of food intake on the drug - drug interaction between two new quinolones, ofloxacin or ciprofloxacin and sucralfate...
2018: Journal of Pharmaceutical Health Care and Sciences
https://www.readbyqxmd.com/read/29785193/gallnuts-a-potential-treasure-in-anticancer-drug-discovery
#16
REVIEW
Jiayu Gao, Xiao Yang, Weiping Yin, Ming Li
Introduction. In the discovery of more potent and selective anticancer drugs, the research continually expands and explores new bioactive metabolites coming from different natural sources. Gallnuts are a group of very special natural products formed through parasitic interaction between plants and insects. Though it has been traditionally used as a source of drugs for the treatment of cancerous diseases in traditional and folk medicinal systems through centuries, the anticancer properties of gallnuts are barely systematically reviewed...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29785119/clinical-relevance-of-lysyl-oxidase-like-2-and-functional-mechanisms-in-glioma
#17
Xiao-Guang Du, Mei-Jia Zhu
Introduction: Glioma is the most frequent malignancy of the adult central nervous system with high recurrence risk and poor prognosis. Understanding the biological molecular mechanisms involved in glioma progression is critical for studying oncogenic mechanisms and improving prognosis. Lysyl oxidase-like 2 (LOXL2) is a kind of lysyl oxidase catalyzing the formation of peptidyl-lysine residues and promoting intramolecular cross-linking, especially for proteins in extracellular matrix. Our study explored the expression pattern of LOXL2 in glioma for the first time and found that its high expression was associated with larger tumor size and advanced tumor grade ( P <0...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29784845/interaction-of-bacterial-phenazines-with-colistimethate-in-bronchial-epithelial-cells
#18
Valeri V Mossine, Deborah L Chance, James K Waters, Thomas P Mawhinney
Multidrug-resistant bacterial infections are being increasingly treated in clinics with polymyxins, a class of antibiotics associated with adverse effects in the kidney, nervous system, or airways of a significant proportion of human and animal patients. Although many of the resistant pathogens display enhanced virulence, a hazard of cytotoxic interactions between polymyxin antibiotics and bacterial virulence factors (VFs) has not been assessed, to date. We report here on testing paired combinations of four Pseudomonas aeruginosa VF phenazine toxins, pyocyanin (PYO), 1-hydroxyphenazine (1-HP), phenazine-1-carboxylic acid (PCA), phenazine-1-carboxamide (PCN), and two commonly prescribed polymyxin drugs, colistimethate (CMS)/colistin and polymyxin B, in three human airway cell lines, BEAS-2B, HBE-1, and CFT-1...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784840/oxidative-stress-and-first-line-antituberculosis-drug-induced-hepatotoxicity
#19
Wing Wai Yew, Kwok Chiu Chang, Denise P Chan
Hepatotoxicity induced by antituberculosis drugs is a serious adverse reaction with significant morbidity and even rarely mortality. This form of toxicity potentially impacts the treatment outcome of tuberculosis in some patients. Confining to first-line antituberculosis drugs, this review addresses whether and how oxidative stress, and more broadly, disturbance in redox homeostasis alongside mitochondrial dysfunction, may contribute to the hepatotoxicity induced by them. Risk factors for such toxicity that have been identified, in addition to genetic factors, principally include old age, malnutrition, alcoholism, chronic hepatitis C and chronic hepatitis B infection, HIV infection and pre-existing liver disease...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784728/cyp2d6-allelic-variants-34-17-2-17-3-and-53-and-a-thr309ala-mutant-display-altered-kinetics-and-nadph-coupling-in-metabolism-of-bufuralol-and-dextromethorphan-and-altered-susceptibility-to-inactivation-by-sch-66712
#20
Sarah M Glass, Cydney M Martell, Alexandria K Oswalt, Victoria Osorio-Vasquez, Christi Cho, Michael J Hicks, Jacqueline M Mills, Rina Fujiwara, Michael J Glista, Sharat S Kamath, Laura Lowe Furge
Metabolic phenotype can be affected by multiple factors including allelic variation and interactions with inhibitors. Human CYP2D6 is responsible for approximately 20% of CYP-mediated drug metabolism but consists of over 100 known variants with several variants being commonly found in the population and others quite rare. Four CYP2D6 allelic variants - three with a series of mutations distal to the active site (*34, *17-2, *17-3) and one ultra-metabolizer with mutations near the active site (*53), along with reference *1 and an active site mutant of *1 (Thr309Ala) were expressed, purified, and studied for interactions with the typical substrates dextromethorphan and bufuralol and the inactivator SCH 66712...
May 21, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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