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https://www.readbyqxmd.com/read/28623936/safety-and-potential-efficacy-of-gemfibrozil-as-a-supportive-treatment-for-children-with-late-infantile-neuronal-ceroid-lipofuscinosis-and-other-lipid-storage-disorders
#1
REVIEW
Kyeongsoon Kim, Hynda K Kleinman, Hahn-Jun Lee, Kalipada Pahan
Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is a group of genetically distinct lysosomal disorders that mainly affect the central nervous system, resulting in progressive motor and cognitive decline primarily in children. Multiple distinct genes involved in the metabolism of lipids have been identified to date with various mutations in this family of diseases. There is no cure for these diseases but some new therapeutic approaches have been tested that offer more hope than the standard palliative care...
June 17, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28547184/combination-of-magnetic-dispersive-micro-solid-phase-extraction-and-supramolecular-solvent-based-microextraction-followed-by-high-performance-liquid-chromatography-for-determination-of-trace-amounts-of-cholesterol-lowering-drugs-in-complicated-matrices
#2
Somayeh Arghavani-Beydokhti, Maryam Rajabi, Alireza Asghari
A novel, efficient, rapid, simple, sensitive, selective, and environmentally friendly method termed magnetic dispersive micro solid-phase extraction combined with supramolecular solvent-based microextraction (Mdμ-SPE-SSME) followed by high-performance liquid chromatography (HPLC) with UV detection is introduced for the simultaneous microextraction of cholesterol-lowering drugs in complicated matrices. In the first microextraction procedure, using layered double hydroxide (LDH)-coated Fe3O4 magnetic nanoparticles, an efficient sample cleanup is simply and rapidly provided without the need for time-consuming centrifugation and elution steps...
May 26, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28534270/occurrence-distribution-and-attenuation-of-pharmaceuticals-and-personal-care-products-in-the-riverside-groundwater-of-the-beiyun-river-of-beijing-china
#3
Lei Yang, Jiang-Tao He, Si-Hui Su, Ya-Feng Cui, De-Liang Huang, Guang-Cai Wang
This study investigated the occurrence, seasonal-spatial distribution characteristics, and attenuation process of 15 pharmaceuticals and personal care products (PPCPs) in riverside sections of Beiyun River of Beijing. The overall PPCP levels both in surface water and riverside groundwater were moderate on the global scale, and showed higher concentrations in the dry season mainly caused by water temperature variation. Caffeine (CF), carbamazepine (CBZ), metoprolol (MTP), N,N-diethyl-meta-toluamide (DEET), diclofenac (DF), bezafibrate (BF), and gemfibrozil (GF) were seven representative PPCPs, because the rest eight studied compounds occurred in low concentrations and less than 15% of the total concentration of PPCPs...
May 23, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28511040/removal-of-selected-ppcps-edcs-and-antibiotic-resistance-genes-in-landfill-leachate-by-a-full-scale-constructed-wetlands-system
#4
Xinzhu Yi, Ngoc Han Tran, Tingru Yin, Yiliang He, Karina Yew-Hoong Gin
Landfill leachate could be a significant source of emerging contaminants (ECs) and antibiotic resistance genes (ARGs) into the environment. This study provides the first information on the occurrence of selected ECs and ARGs in raw leachate from 16-year old closed landfill site in Singapore. Among the investigated ECs, acetaminophen (ACT), bisphenol A (BPA), clofibric acid (CA), caffeine (CF), crotamiton (CTMT), diclofenac (DCF), N,N-diethyl-m-toluamide (DEET), gemfibrozil (GFZ), lincomycin (LIN), salicylic acid (SA), and sulfamethazine (SMZ) were the most frequently detected compounds in raw landfill leachate...
May 8, 2017: Water Research
https://www.readbyqxmd.com/read/28505885/occurrence-and-environmental-impact-of-pharmaceutical-residues-from-conventional-and-natural-wastewater-treatment-plants-in-gran-canaria-spain
#5
C Afonso-Olivares, Z Sosa-Ferrera, J J Santana-Rodríguez
The presence and fate of pharmaceutical residues in environmental samples are of great interest. There is a vast number of studies published regarding their input, presence, effects and risks in ecosystems. Moreover, it has been demonstrated that the primary source of input of these contaminants in the environment is from Wastewater Treatment Plants (WWTPs). It is therefore essential to evaluate the efficiency of commonly used treatments and the necessity of applying novel purification processes in order to eliminate or reduce the concentration of pharmaceuticals from wastewater or from the effluent of WWTPs...
December 1, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28479356/quantitative-analysis-of-complex-drug-drug-interactions-between-repaglinide-and-cyclosporin-a-gemfibrozil-using-physiologically-based-pharmacokinetic-models-with-in-vitro-transporter-enzyme-inhibition-data
#6
Soo-Jin Kim, Kota Toshimoto, Yoshiaki Yao, Takashi Yoshikado, Yuichi Sugiyama
Quantitative analysis of transporter- and enzyme-mediated complex drug-drug interactions (DDIs) is challenging. Repaglinide (RPG) is transported into the liver by OATP1B1 and then is metabolized by CYP2C8 and CYP3A4. The purpose of this study is to describe the complex DDIs of RPG quantitatively based on unified physiologically-based pharmacokinetic (PBPK) models using in vitro Ki values for OATP1B1, CYP3A4, and/or CYP2C8. Cyclosporin A (CsA) or gemfibrozil (GEM) increased the blood concentrations of RPG. The time profiles of RPG and the inhibitors were analyzed by PBPK models, considering the inhibition of OATP1B1 and CYP3A4 by CsA, or OATP1B1 inhibition by GEM and its glucuronide and the mechanism-based inhibition of CYP2C8 by GEM glucuronide...
May 4, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28453252/polymer-inclusion-membranes-with-condensed-phase-membrane-introduction-mass-spectrometry-cp-mims-improved-analytical-response-time-and-sensitivity
#7
Gregory W Vandergrift, Erik T Krogh, Chris G Gill
Condensed phase membrane introduction mass spectrometry (CP-MIMS) is an online, in situ analysis technique for low volatility analytes. Analytes diffuse through a hollow fiber membrane, where they are then dissolved by a liquid (condensed) acceptor phase flowing through the membrane lumen. Permeating analytes are entrained to an atmospheric pressure ionization source for subsequent measurement by a mass spectrometer. Larger analytes, with inherently lower diffusivities, suffer from lengthy response times and lower sensitivity, limiting the use of CP-MIMS for their online, real-time measurement...
May 5, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28444890/utilizing-pbpk-modeling-to-evaluate-the-potential-of-a-significant-drug-drug-interaction-between-clopidogrel-and-dasabuvir-a-scientific-perspective
#8
V Arya, P Zhao, K S Reynolds, P Mishra, I R Younis
Dasabuvir, a component of VIEKIRA PAK, is a substrate of CYP2C8 enzymes. Prescribing information for VIEKIRA PAK contraindicates gemfibrozil, a strong CYP2C8 inhibitor, because coadministration significantly increases dasabuvir exposures, which may increase the risk of QT prolongation. Clopidogrel may increase dasabuvir exposures primarily due to CYP2C8 inhibition by clopidogrel-acyl-β-D-glucuronide. This commentary outlines the US Food and Drug Administration (FDA) interdisciplinary review team's scientific perspective to address the potential for a significant drug-drug interaction (DDI) between clopidogrel and VIEKIRA PAK...
April 26, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28414683/recurrent-hypertriglyceridemic-pancreatitis-htgp-and-the-use-of-insulin-drip-as-treatment
#9
T Tran, N Lee
INTRODUCTION: Chronic pancreatitis by definition is a recurrent episode of acute pancreatitis and is commonly associated with alcoholism in the US. Another cause of chronic pancreatitis is hypertriglyceridemia (HTGP);, occurring in 1-5 percent of cases. The incidence of HTGP is higher in patients with diabetes and HIV, usually requiring triglyceride levels > 1000 mg/dL. CASE: A 33 year old man with uncontrolled type 1 diabetes and recurrent pancreatitis, first diagnosed 5 years prior, presented as a transfer from an outside hospital for a recurrent episode of HTGP...
March 2017: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
https://www.readbyqxmd.com/read/28401920/occurrence-of-fibrates-and-their-metabolites-in-source-and-drinking-water-in-shanghai-and-zhejiang-china
#10
Akiko Ido, Youhei Hiromori, Liping Meng, Haruki Usuda, Hisamitsu Nagase, Min Yang, Jianying Hu, Tsuyoshi Nakanishi
Fibrates, which are widely used lipidaemic-modulating drugs, are emerging environmental pollutants. However, fibrate concentrations in the environment have not been thoroughly surveyed. Here, we determined concentrations of the most commonly used fibrates and their metabolites in source water and drinking water samples from ten drinking water treatment plants in Shanghai and Zhejiang, China, using solid-phase extraction and liquid chromatography-tandem mass spectrometry. All the target compounds were detected in at least some of the source water samples, at concentrations ranging from 0...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28374976/ppar%C3%AE-activation-suppresses-cytochrome-p450-induction-potential-in-mice-treated-with-gemfibrozil
#11
Cunzhong Shi, Luo Min, Julin Yang, Manyun Dai, Danjun Song, Huiying Hua, Gangming Xu, Frank J Gonzalez, Aiming Liu
Gemfibrozil, a peroxisome proliferator-activated receptor α (PPARα) agonist, is widely used for hypertriglyceridaemia and mixed hyperlipidaemia. Drug-drug interaction of gemfibrozil and other PPARα agonists has been reported. However, the role of PPARα in Cytochrome P450 (CYP) induction by fibrates is not well known. In this study, wild-type mice were first fed gemfibrozil-containing diets (0.375%, 0.75% and 1.5%) for 14 days to establish a dose-response relationship for CYP induction. Then, wild-type mice and Pparα-null mice were treated with a 0...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28343425/ppar-%C3%AE-agonists-are-still-on-the-rise-an-update-on-clinical-and-experimental-findings
#12
REVIEW
Nicola Ferri, Alberto Corsini, Cesare Sirtori, Massimiliano Ruscica
Non-fasting plasma triglyceride (TG) and remnant cholesterol levels, cholesterol content of triglyceride-rich lipoproteins, have been suggested to be an additional cause of cardiovascular diseases; thus, pharmacological TG-lowering with fibrates, activators of PPAR-alpha system, has been linked to risk reduction. Areas covered: This manuscript reviews available evidence on clinical trials involving highly selective PPAR-α agonists (i.e., pemafibrate) and drugs used in the pre-clinical and experimental setting (e...
May 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28340451/the-role-of-drug-drug-interactions-in-prostate-cancer-treatment-focus-on-abiraterone-acetate-prednisone-and-enzalutamide
#13
REVIEW
Marzia Del Re, Stefano Fogli, Lisa Derosa, Francesco Massari, Paul De Souza, Stefania Crucitta, Sergio Bracarda, Daniele Santini, Romano Danesi
Elderly patients with cancer may have comorbidities, each requiring additional pharmacologic treatment. Therefore, the occurrence of pharmacokinetic (PK) and pharmacodynamic (PD) interactions is very likely, and the risk of adverse reactions (ADRs), due to the narrow therapeutic window of anticancer drugs, is increased. Drug-drug interactions (DDIs) may occur in prostate cancer patients due to inhibition by abiraterone of liver cytochrome P450 (CYP)-dependent enzymes CYP2C8 and 2D6, which are involved in the metabolism of approximately 25% of all drugs, and induction by enzalutamide of CYP3A4, 2C9 and 2C19, which metabolize up to 50% of medications...
March 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28296193/investigating-transporter-mediated-drug-drug-interactions-using-a-physiologically-based-pharmacokinetic-model-of-rosuvastatin
#14
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...
April 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28284639/transport-behavior-of-the-pharmaceutical-compounds-carbamazepine-sulfamethoxazole-gemfibrozil-ibuprofen-and-naproxen-and-the-lifestyle-drug-caffeine-in-saturated-laboratory-columns
#15
Klaus H Hebig, Laura G Groza, Michelle J Sabourin, Traugott J Scheytt, Carol J Ptacek
Despite the large number of pharmaceutically active compounds found in natural environments little is known about their transport behavior in groundwater, which is complicated by their wide range of physical and chemical properties. The transport behavior of five widely used and often detected pharmaceutical compounds and one lifestyle drug has therefore been investigated, using a set of three column experiments. The investigated compounds were the anticonvulsant carbamazepine, the lifestyle drug caffeine, the antibiotic sulfamethoxazole, the lipid regulator gemfibrozil, and the nonsteroidal anti-inflammatories ibuprofen and naproxen...
March 8, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28199788/development-of-fluorescence-surrogates-to-predict-the-photochemical-transformation-of-pharmaceuticals-in-wastewater-effluents
#16
Shuwen Yan, Bo Yao, Lushi Lian, Xinchen Lu, Shane A Snyder, Rui Li, Weihua Song
The photochemical transformation of pharmaceutical and personal care products (PPCPs) in wastewater effluents is an emerging concern for environmental scientists. In the current study, the photodegradation of 29 PPCPs was examined in effluents under simulated solar irradiation. Direct photodegradation, triplet state effluent organic matter ((3)EfOM*)-mediated and hydroxyl radical (HO(•))-mediated degradation are three major pathways in the removal process. With the photodegradation of trace levels of PPCPs, the excitation-emission matrix (EEM) fluorescence intensities of the effluents were also gradually reduced...
March 7, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28199020/gemfibrozil-food-and-drug-administration-approved-lipid-lowering-drug-increases-longevity-in-mouse-model-of-late-infantile-neuronal-ceroid-lipofuscinosis
#17
Arunava Ghosh, Suresh Babu Rangasamy, Khushbu K Modi, Kalipada Pahan
Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL) is a rare neurodegenerative disease caused by mutations in the Cln2 gene that leads to deficiency or loss of function of the tripeptidyl peptidase 1 (TPP1) enzyme. TPP1 deficiency is known to cause the accumulation of autofluoroscent lipid-protein pigments in brain. Similar to other neurodegenerative disorders, LINCL is also associated with neuroinflammation and neuronal damage. Despite investigations, no effective therapy is currently available for LINCL...
May 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28065762/characterisation-of-early-changes-in-ovine-cln5-and-cln6-batten-disease-neural-cultures-for-the-rapid-screening-of-therapeutics
#18
Hannah L Best, Nicole J Neverman, Hollie E Wicky, Nadia L Mitchell, Beulah Leitch, Stephanie M Hughes
Batten disease (neuronal ceroid lipofuscinosis) refers to a group of neurodegenerative lysosomal storage diseases predominantly affecting children. There are currently no effective treatments, and the functions of many of the associated gene products are unknown. Here we characterise fetal neural cultures from two genetically distinct sheep forms of Batten disease, with mutations in the lysosomal protein encoding gene CLN5 and endoplasmic reticulum membrane protein encoding gene CLN6, respectively. We found similar reductions in autophagy, acidic organelles and synaptic recycling in both forms compared to unaffected cells...
January 5, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28057168/evaluation-and-optimization-of-blood-micro-sampling-methods-serial-sampling-in-a-cross-over-design-from-an-individual-mouse
#19
Nita J Patel, Enaksha Wickremsinhe, Yu-Hua Hui, Alexandar Barr, Nicholas Masterson, Kenneth Ruterbories, Jennifer Weller, Jennifer Hanes, Tom Kern, Everett Perkins
PURPOSE: Current practices applied to mouse pharmacokinetic (PK) studies often use large numbers of animals with sporadic or composite sampling that inadequately describe PK profiles.  The purpose of this work was to evaluate and optimize blood microsampling techniques coupled with dried blood spot (DBS) and LC-MS/MS analysis to generate reliable PK data in mice.  In addition, the feasibility of cross-over designs was assessed and recommendations are presented. METHODS: The work describes a comprehensive evaluation of five blood microsampling techniques (tail clip, tail vein with needle hub, submandibular, retro-orbital, and saphenous bleeding) in CD-1 mice...
October 2016: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27987461/modelling-the-photochemical-attenuation-pathways-of-the-fibrate-drug-gemfibrozil-in-surface-waters
#20
Debora Fabbri, Valter Maurino, Marco Minella, Claudio Minero, Davide Vione
Gemfibrozil (GFZ) is a relatively persistent pollutant in surface-water environments and it is rather recalcitrant to biological degradation. The GFZ photochemical lifetimes are relatively short in shallow waters with low levels of dissolved organic carbon (DOC), but they can reach the month-year range in deep and high-DOC waters. The main reason is that GFZ undergoes negligible reaction with singlet oxygen or degradation sensitised by the triplet states of chromophoric dissolved organic matter, which are the usually prevalent photochemical pathways in deep and high-DOC sunlit waters...
March 2017: Chemosphere
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