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https://www.readbyqxmd.com/read/29784023/delayed-presentation-of-severe-rhabdomyolysis-leading-to-acute-kidney-injury-following-atorvastatin-gemfibrozil-combination-therapy-a-case-report
#1
Chamara Dalugama, Manoji Pathirage, S A M Kularatne
BACKGROUND: Rhabdomyolysis is a rare but serious complication of lipid-lowering therapy. Statin and fibrate combination increases the risk of rhabdomyolysis possibly by pharmacodynamic interactions. Advanced age, diabetes, hypothyroidism, polypharmacy, and renal impairment are known to increase the risk of rhabdomyolysis. Management strategies include fluid resuscitation and urine alkalinization. Renal indications such as refractory hyperkalemia, acidosis, fluid overload, or uremic complications mandate renal replacement therapy in rhabdomyolysis...
May 22, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29779093/pharmacokinetics-of-the-novel-selective-non-steroidal-mineralocorticoid-receptor-antagonist-finerenone-in-healthy-volunteers-results-from-an-absolute-bioavailability-study-and-drug-drug-interaction-studies-in-vitro-and-in-vivo
#2
Roland Heinig, Michael Gerisch, Anna Engelen, Johannes Nagelschmitz, Stephanie Loewen
BACKGROUND AND OBJECTIVES: Finerenone is a selective, non-steroidal mineralocorticoid receptor antagonist. In vivo and in vitro studies were performed to assess absolute bioavailability of finerenone, the effect of metabolic enzyme inhibitors on the pharmacokinetics of finerenone and its metabolites, the quantitative contribution of the involved enzymes cytochrome P450 (CYP) 3A4 and CYP2C8 and the relevance of gut wall versus liver metabolism. METHODS: The pharmacokinetics, safety and tolerability of finerenone (1...
May 19, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29743187/the-effects-of-farnesoid-x-receptor-activation-on-arachidonic-acid-metabolism-nf-kb-signaling-and-hepatic-inflammation
#3
Zhibo Gai, Michele Visentin, Ting Gui, Lin Zhao, Wolfgang E Thasler, Stephanie Hausler, Ivan Hartling, Alessio Cremonesi, Christian Hiller, Gerd A Kullak-Ublick
Inflammation has a recognized role in non-alcoholic fatty liver disease (NAFLD) progression. The present work studied the effect of high fat diet (HFD) on arachidonic acid metabolism in the liver and investigated the role of the farnesoid X receptor (FXR, NR1H4) in eicosanoid biosynthetic pathways and NF-kB signaling, major modulators of the inflammatory cascade. Mice were fed a HFD to induce NAFLD, then, treated with the FXR ligand obeticholic acid (OCA). Histology and gene expression analysis were performed on liver tissue...
May 9, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29712725/quantitative-analysis-of-complex-drug-drug-interactions-ddis-between-cerivastatin-and-inhibitors-using-physiologically-based-pharmacokinetic-pbpk-modeling
#4
Yoshiaki Yao, Kota Toshimoto, Soo-Jin Kim, Takashi Yoshikado, Yuichi Sugiyama
Cerivastatin (CER) was withdrawn from the world market because of lethal rhabdomyolysis. Coadministrations of CER and cyclosporine A (CsA) or gemfibrozil (GEM) have been reported to increase the CER blood concentration. CsA is an inhibitor of OATP1B1 and CYP3A4, and GEM and its glucuronide (GEM-glu) inhibit OATP1B1 and CYP2C8. The purpose of this study was to describe the transporter-/enzymemediated drug-drug interactions (DDIs) of CER with CsA or GEM based on unified physiologically based pharmacokinetic (PBPK) models and to investigate whether the DDIs can be quantitatively analyzed by a bottom-up approach...
April 30, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29707997/effect-of-combination-sildenafil-and-gemfibrozil-on-cisplatin-induced-nephrotoxicity-role-of-heme-oxygenase-1
#5
Safaa Behiry, Ahmed Rabie, Mahmoud Kora, Wesam Ismail, Dina Sabry, Ahmed Zahran
BACKGROUND/AIM: Cisplatin-induced nephrotoxicity in large proportion of patients. The aim of this work is to clarify the effect of combination of sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity either before or after cisplatin treatment and determination of nephrotoxicity predictors among the measured tissue markers. METHODS: Thirty two adult male albino rats were divided into four equal groups (G) GI control, GII received cisplatin, GIII received sildenafil and gemfibrozil before cisplatin, GIV received sildenafil and gemfibrozil after cisplatin...
November 2018: Renal Failure
https://www.readbyqxmd.com/read/29681002/the-influence-of-fibrate-initiation-on-inr-and-warfarin-dose-in-patients-receiving-chronic-warfarin-therapy
#6
John F Polnak, Thomas Delate, Nathan P Clark
Several drug interaction compendia report a risk of warfarin potentiation after initiation of a fibrate; however, the evidence of this interaction is limited. The objective of this study was to evaluate warfarin dose and international normalized ratio (INR) response among a large sample of patients receiving chronic warfarin who initiated a fibrate. This was a retrospective, one-sample, pre-to-post study. Adult patients who were receiving chronic warfarin therapy at the time of gemfibrozil or fenofibrate dispensing between 1/1/2000 and 3/31/2016 were included...
April 21, 2018: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29662003/ppar-agonists-and-metabolic-syndrome-an-established-role
#7
REVIEW
Margherita Botta, Matteo Audano, Amirhossein Sahebkar, Cesare R Sirtori, Nico Mitro, Massimiliano Ruscica
Therapeutic approaches to metabolic syndrome (MetS) are numerous and may target lipoproteins, blood pressure or anthropometric indices. Peroxisome proliferator-activated receptors (PPARs) are involved in the metabolic regulation of lipid and lipoprotein levels, i.e., triglycerides (TGs), blood glucose, and abdominal adiposity. PPARs may be classified into the α, β/δ and γ subtypes. The PPAR-α agonists, mainly fibrates (including newer molecules such as pemafibrate) and omega-3 fatty acids, are powerful TG-lowering agents...
April 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29574201/enhanced-pharmaceutical-removal-from-water-in-a-three-step-bio-ozone-bio-process
#8
Arnoud de Wilt, Koen van Gijn, Tom Verhoek, Amber Vergnes, Mirit Hoek, Huub Rijnaarts, Alette Langenhoff
Individual treatment processes like biological treatment or ozonation have their limitations for the removal of pharmaceuticals from secondary clarified effluents with high organic matter concentrations (i.e. 17 mg TOC/L). These limitations can be overcome by combining these two processes for a cost-effective pharmaceutical removal. A three-step biological-ozone-biological (BO3 B) treatment process was therefore designed for the enhanced pharmaceutical removal from wastewater effluent. The first biological step removed 38% of ozone scavenging TOC, thus proportionally reducing the absolute ozone input for the subsequent ozonation...
March 12, 2018: Water Research
https://www.readbyqxmd.com/read/29574198/pilot-scale-evaluation-of-micropollutant-abatements-by-conventional-ozonation-uv-o-3-and-an-electro-peroxone-process
#9
Weikun Yao, Syed Waqi Ur Rehman, Huijiao Wang, Hongwei Yang, Gang Yu, Yujue Wang
The electro-peroxone (E-peroxone) process is an emerging ozone-based advanced oxidation process (AOP) that has shown large potential for micropollutant abatement in water treatment. To evaluate its performance under more realistic conditions of water treatment, a continuous-flow pilot E-peroxone system was developed and compared with conventional ozonation and a UV/O3 process for micropollutant abatements in various water matrices (groundwater, surface water, and secondary wastewater effluent) in this study...
March 16, 2018: Water Research
https://www.readbyqxmd.com/read/29557210/the-emerging-role-of-inflammation-in-cardiovascular-disease
#10
Brandon K Martinez, C Michael White
OBJECTIVE: To review the role of inflammatory suppression in patients with atherosclerotic cardiovascular disease (ASCVD) with a focus on the interleukin-1β blocker canakinumab. DATA SOURCES: An Ovid MEDLINE literature search (1946 to February 2018) was performed using search terms inflammation, ASCVD, atherosclerosis, C-reactive protein, canakinumab. Additional references were identified from a review of literature citations. STUDY SELECTION AND DATA EXTRACTION: English-language studies assessing the impact of pharmacological agents, including canakinumab, on inflammation as measured by high-sensitivity C-reactive protein (hsCRP) and the association with reducing ASCVD events were evaluated...
March 1, 2018: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29550727/degradation-of-lipid-regulators-by-the-uv-chlorine-process-radical-mechanisms-chlorine-oxide-radical-clo-%C3%A2-mediated-transformation-pathways-and-toxicity-changes
#11
Xiujuan Kong, Zihao Wu, Ziran Ren, Kaiheng Guo, Shaodong Hou, Zhechao Hua, Xuchun Li, Jingyun Fang
Degradation of three lipid regulators, i.e., gemfibrozil, bezafibrate and clofibric acid, by a UV/chlorine treatment was systematically investigated. The chlorine oxide radical (ClO• ) played an important role in the degradation of gemfibrozil and bezafibrate with second-order rate constants of 4.2 (±0.3) × 108  M-1  s-1 and 3.6 (±0.1) × 107  M-1  s-1 , respectively, whereas UV photolysis and the hydroxyl radical (HO• ) mainly contributed to the degradation of clofibric acid. The first-order rate constants (k') for the degradation of gemfibrozil and bezafibrate increased linearly with increasing chlorine dosage, primarily due to the linear increase in the ClO• concentration...
June 15, 2018: Water Research
https://www.readbyqxmd.com/read/29534628/gemfibrozil-has-antidepressant-effects-in-mice-involvement-of-the-hippocampal-brain-derived-neurotrophic-factor-system
#12
Yu-Fei Ni, Hao Wang, Qiu-Yan Gu, Fei-Ying Wang, Ying-Jie Wang, Jin-Liang Wang, Bo Jiang
Major depressive disorder has become one of the most serious neuropsychiatric disorders worldwide. However, currently available antidepressants used in clinical practice are ineffective for a substantial proportion of patients and always have side effects. Besides being a lipid-regulating agent, gemfibrozil is an agonist of peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the antidepressant effects of gemfibrozil on C57BL/6J mice using the forced swim test (FST) and tail suspension test (TST), as well as the chronic unpredictable mild stress (CUMS) model of depression...
April 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29494905/investigation-of-biotransformation-sorption-and-desorption-of-multiple-chemical-contaminants-in-pilot-scale-drinking-water-biofilters
#13
Katherine E Greenstein, Julia Lew, Eric R V Dickenson, Eric C Wert
The evolving demands of drinking water treatment necessitate processes capable of removing a diverse suite of contaminants. Biofiltration can employ biotransformation and sorption to remove various classes of chemicals from water. Here, pilot-scale virgin anthracite-sand and previously used biological activated carbon (BAC)-sand dual media filters were operated for ∼250 days to assess removals of 0.4 mg/L ammonia as nitrogen, 50-140 μg/L manganese, and ∼100 ng/L each of trace organic compounds (TOrCs) spiked into pre-ozonated Colorado River water...
June 2018: Chemosphere
https://www.readbyqxmd.com/read/29494825/gemfibrozil-and-carbamazepine-decrease-steroid-production-in-zebrafish-testes-danio-rerio
#14
Shamaila Fraz, Abigail H Lee, Joanna Y Wilson
Gemfibrozil (GEM) and carbamazepine (CBZ) are two environmentally relevant pharmaceuticals and chronic exposure of fish to these compounds has decreased androgen levels and fish reproduction in laboratory studies. The main focus of this study was to examine the effects of GEM and CBZ on testicular steroid production, using zebrafish as a model species. Chronic water borne exposures of adult zebrafish to 10 μg/L of GEM and CBZ were conducted and the dosing was confirmed by chemical analysis of water as 17...
May 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29476970/investigation-of-pharmaceutically-active-compounds-in-an-urban-receiving-water-occurrence-fate-and-environmental-risk-assessment
#15
Jianchao Liu, Xiaoxiang Dan, Guanghua Lu, Jie Shen, Donghai Wu, Zhenhua Yan
Pharmaceutically active compounds (PhACs) recently have been recognized to constitute a health risk for aquatic ecosystems. The major pathways of PhACs to enter the aquatic environment are excretion and discharge of effluents through sewage treatment plants (STPs). The occurrence, bioaccumulation and risk assessment of lipophilic PhACs, including erythromycin, ketoconazole, indomethacin, diclofenac, gemfibrozil, bezafibrate, propranolol, carbamazepine, sertraline and 17α-ethinylestradiol were investigated in a river that receives effluents from STP...
June 15, 2018: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29476637/the-effects-of-parental-carbamazepine-and-gemfibrozil-exposure-on-sexual-differentiation-in-zebrafish-danio-rerio
#16
Kristine M Hammill, Shamaila Fraz, Abigail H Lee, Joanna Y Wilson
The effects of parental exposure to pharmaceuticals on sexual differentiation in F1 offspring were examined in zebrafish (Danio rerio). Adult zebrafish were exposed to 0 or 10 μg/L of carbamazepine or gemfibrozil for 6 wk and bred in pairwise crosses to generate 7 distinct lineages. Lineages were formed with both parents from the same treatment group or with only one parent exposed, to delineate between maternal and paternal effects. The F1 offspring from each lineage were reared in clean water and sampled at 45 and 60 d post fertilization (dpf)...
February 24, 2018: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/29381228/implications-of-intercorrelation-between-hepatic-cyp3a4-cyp2c8-enzymes-for-the-evaluation-of-drug-drug-interactions-a-case-study-with-repaglinide
#17
Kosuke Doki, Adam S Darwich, Brahim Achour, Aleksi Tornio, Janne T Backman, Amin Rostami-Hodjegan
AIMS: Statistically significant positive correlations are reported for the abundance of hepatic drug-metabolizing enzymes. We investigate, as an example, the impact of CYP3A4-CYP2C8 intercorrelation on the predicted interindividual variabilities of clearance and drug-drug interactions (DDIs) for repaglinide using physiologically based pharmacokinetic (PBPK) modelling. METHODS: PBPK modelling and simulation were employed using Simcyp Simulator (v15.1). Virtual populations were generated assuming intercorrelations between hepatic CYP3A4-CYP2C8 abundances derived from observed values in 24 human livers...
May 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29276238/treatment-of-hypertriglyceridemia-induced-acute-pancreatitis-with-insulin-heparin-and-gemfibrozil-a-case-series
#18
Drayton A Hammond, Laura Finlay
Hypertriglyceridemia is the third most common worldwide cause of acute pancreatitis. Resolving the underlying etiology is imperative for optimal management. This is especially true with regard to hypertriglyceridemia, as this etiology may cause more severe acute pancreatitis and worse symptoms than other causes of the disease. Many pharmacological treatment options for hypertriglyceridemia-induced acute pancreatitis (HTGP) have been proposed; however, the safety and efficacy for specific treatment regimens remain nebulous...
November 2017: Hospital Pharmacy
https://www.readbyqxmd.com/read/29240983/human-ugt2b7-is-the-major-isoform-responsible-for-the-glucuronidation-of-clopidogrel-carboxylate
#19
Jin-Zi Ji, Bei-Bei Huang, Tong-Tong Gu, Ting Tai, Huan Zhou, Yu-Meng Jia, Qiong-Yu Mi, Meng-Ran Zhang, Hong-Guang Xie
Clopidogrel is predominantly hydrolyzed to clopidogrel carboxylic acid (CCA) by carboxylesterase 1, and subsequently CCA is glucuronidated to clopidogrel acyl glucuronide (CAG) by uridine diphosphate-glucuronosyltransferases (UGTs); however, the UGT isoenzymes glucuronidating CCA remain unidentified to date. In this study, the glucuronidation of CCA was screened with pooled human liver microsomes (HLMs) and 7 human recombinant UGT (rUGT) isoforms. Results indicated that rUGT2B7 exhibited the highest catalytical activity for the CCA glucuronidation as measured with a mean Vmax value of 120...
February 2018: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29168700/photodegradation-of-some-brominated-and-phenolic-micropollutants-in-raw-hospital-wastewater-with-ceo-2-and-tio-2-nanoparticles
#20
Delia Teresa Sponza, Gökçe Güney
In this study, the degradations of 2,3,4,5,6-pentabromotoluene (PBT), 2,3,4,5,6-pentabromoethyl benzene (PBEB), triclosan (TCS) and gemfibrozil (GFZ) in raw hospital wastewater were investigated with cerium (IV) oxide and titanium (IV) oxide nanoparticles considering the mechanisms of adsorption, photolysis, and photocatalysis with UV-C lamps. The effects of nano-CeO2 and nano-TiO2 concentrations, irradiation times, UV light powers and hospital wastewater pH on the photodegradation yields of micropollutants namely PBT, PBEB, TCS and GFZ were investigated throughout photocatalysis...
November 2017: Water Science and Technology: a Journal of the International Association on Water Pollution Research
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