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https://www.readbyqxmd.com/read/28432691/tenapanor-administration-and-the-activity-of-the-h-coupled-transporter-pept1-in-healthy-volunteers
#1
Susanne Johansson, David P Rosenbaum, Johan Palm, Bergur Stefansson, Mikael Knutsson, Eleanor A Lisbon, Constanze Hilgendorf
AIM: Tenapanor (RDX5791/AZD1722), an inhibitor of gastrointestinal Na(+) /H(+) exchanger NHE3, is being evaluated for the treatment of patients with constipation-predominant irritable bowel syndrome and the treatment of hyperphosphataemia in patients with chronic kidney disease on dialysis. By reducing intestinal H(+) secretion, inhibition of NHE3 by tenapanor could indirectly affect H(+) -coupled transporter activity, leading to drug-drug interactions. We investigated the effect of tenapanor on the activity of the H(+) -coupled peptide transporter PepT1 via assessment of the pharmacokinetics of cefadroxil - a compound transported by PepT1 - in healthy volunteers...
April 22, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28430301/towards-a-bioengineered-kidney-recellularization-strategies-for-decellularized-native-kidney-scaffolds
#2
Michele Fedecostante, Oana G Onciu, Koen G C Westphal, Rosalinde Masereeuw
Patients with end-stage renal disease often undergo dialysis as a partial substitute for kidney function while waiting for their only treatment option: a kidney transplant. Several research directions emerged for alternatives in support of the ever-growing numbers of patients. Recent years brought big steps forward in the field, with researchers questioning and improving the current dialysis devices as well as moving towards the design of a bioengineered kidney. Whole-organ engineering is also being explored as a possibility, making use of animal or human kidney scaffolds for engineering a transplantable organ...
April 20, 2017: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28429551/the-role-of-calcium-and-non-calcium-based-phosphate-binders-in-chronic-kidney-disease
#3
Grahame J Elder, Jacqueline Center
Rising levels of serum phosphate occur late in the course of chronic kidney disease (CKD) and have been easy targets for nephrologists to treat using phosphate binding drugs, as well as fertile ground for the pharmaceutical industry, for meta-analysis and for the earnest pontifications of guideline writers. Unfortunately, the evidence does little to support this focus, which might be better applied to earlier, adaptive hormonal changes, and to phosphate balance rather than serum phosphate levels. Nevertheless, phosphate binders are ubiquitously prescribed to patients on dialysis, and often prescribed to patients with earlier stages of CKD; for which there is no evidence of benefit and some evidence that calcium-based binders (CBBs) and possibly non-CBBs may cause more harm than placebo...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28416553/pharmacokinetics-and-dialytic-clearance-of-ceftazidime-avibactam-in-a-critically-ill-patient-on-continuous-venovenous-hemofiltration
#4
Eric Wenzler, Kristen L Bunnell, Susan C Bleasdale, Scott Benken, Larry H Danziger, Keith A Rodvold
Ceftazidime-avibactam 1.25 g every 8 hours was used to treat multi-drug resistant Pseudomonas aeruginosa bacteremia in a critically ill patient on continuous venovenous hemofiltration (CVVH). Pre-filter plasma drug concentrations of ceftazidime and avibactam were measured at 0, 1, 2, 4, 6, and 8 hours along with post-filter and ultrafiltrate concentrations at hours 2 and 6. Plasma pharmacokinetic parameters of ceftazidime and avibactam, respectively, were Cmax 61.10 and 14.54 mg/L, Cmin 31.96 and 8.45 mg/L, t1/2 6...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28415422/synthesis-and-characterization-of-redox-sensitive-heparin-%C3%AE-sitosterol-micelles-their-application-as-carriers-for-the-pharmaceutical-agent-doxorubicin-and-investigation-of-their-antimetastatic-activities-in-vitro
#5
Tilahun Ayane Debele, Shewaye Lakew Mekuria, Hsieh-Chih Tsai
Although there are several clinical attempts to treat tumors at the primary site, only few therapies can inhibit the spread of metastatic cancers. In this study, we synthesized redox-sensitive heparin-β-sitosterol micelles that show antimetastatic activity. Proton nuclear magnetic resonance and Fourier transform infrared analyses confirmed the formation of bioreducible heparin-β-sitosterol (bHSC) conjugates, whereas dynamic light scattering was used to measure the particle size and zeta potential. Both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assays confirmed the low toxicity of the synthesized micelles...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28414145/real-time-analysis-of-tenofovir-release-kinetics-using-quantitative-phosphorus-31-p-nuclear-magnetic-resonance-spectroscopy
#6
Vivek Agrahari, Jianing Meng, Sudhaunshu S Purohit, Nathan A Oyler, Bi-Botti C Youan
The dialysis method is classically used for drug separation before analysis, but, does not provide direct and real-time drug quantification and has limitations affecting the dialysis rate. In this study, a phosphorus nuclear magnetic resonance ((31)P-qNMR) method is developed for the real-time quantification of therapeutic molecules in vitro. The release kinetics of model drug tenofovir (TFV: anti-HIV microbicide) was analyzed in vaginal fluid simulant (VFS), semen fluid simulant (SFS), and human plasma (HP) from chitosan nanofibers (size ∼100-200nm) using the NMR (direct) method and compared with dialysis/UV-Vis (indirect) method...
April 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28413966/the-clinical-problems-of-hypertension-treatment-in-hemodialysis-patients
#7
Charalampos N Loutradis, Costas Tsioufis, Pantelis A Sarafidis
Hypertension (HT) is present in more than 80% of patients undergoing hemodialysis (HD). Elevated blood pressure (BP) in hemodialysis patients is associated with cardiovascular events and mortality only when BP is recorded with home or ambulatory monitoring, since pre- and post-dialysis measurements are not valid estimates of BP levels during the inter-dialytic interval. Sodium and water overload is the most important of several mechanisms involved in HT development in HD. In this context, non-pharmacologic measures to ensure water and sodium balance by achieving patient dry weight and decreasing daily sodium intake, through modification of sodium level in the diet or in dialysis dialysate, are fundamental for HT control...
April 14, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28407764/severe-hypertriglyceridemia-secondary-to-venlafaxine-use-in-an-older-adult-on-dialysis-case-report
#8
Hsiang-Wen Lin, Cory A Simonavice, Chiung-Ray Lu, Wen-Ling Lin, Po-Lun Wu, Che-Yi Chou, Chun-Hui Liao, Hsieh-Yuan Lane
BACKGROUND: Although the prescribing information for Venlafaxine extended release includes a discussion about possible increases in total cholesterol and triglycerides (TG) seen in healthier adult patients during premarketing clinical trials, no post-marketing studies or case reports, that discuss the effects of venlafaxine on TG in elderly patients with chronic kidney disease. CASE PRESENTATION: We report a 71 year-old male patient with end-stage renal disease on hemodialysis, with a history of coronary artery disease, mild hyperlipidemia, and hypertension...
April 13, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28407286/pet-imaging-with-copper-64-as-a-tool-for-real-time-in-vivo-investigations-of-the-necessity-for-crosslinking-of-polymeric-micelles-in-nanomedicine
#9
Andreas I Jensen, Tina Binderup, Pramod Kumar Ek, Constance E Grandjean, Palle H Rasmussen, Andreas Kjaer, Thomas L Andresen
Polymeric micelles in nanomedicine are often crosslinked to prevent disintegration in vivo. This typically requires clinically problematic chemicals or laborious procedures. In addition, crosslinking may interfere with advanced release strategies. Despite this, it is often not investigated whether crosslinking is necessary for efficient drug delivery. We used PET imaging with (64) Cu to demonstrate general methodology for real-time in vivo investigations of micelle stability. Triblock copolymers with 4-methylcoumarin cores of ABC-type (PEG-PHEMA-PCMA) were functionalized in the handle region (PHEMA) with CB-TE2A chelators...
April 13, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28396747/optimization-of-anti-infective-dosing-regimens-during-online-haemodiafiltration
#10
Nynke G L Jager, Anthe S Zandvliet, Daniel J Touw, Erik L Penne
Online haemodiafiltration (HDF) is increasingly used in clinical practice as a routine intermittent dialysis modality. It is well known that renal impairment and renal replacement therapy can substantially affect the pharmacokinetic behaviour of several drugs. However, surprisingly few data are available on the need for specific dose adjustments during HDF. Due to convection, drug clearance may be increased during HDF as compared with standard haemodialysis. This may be of particular interest in patients undergoing anti-infective therapy, since under-dosing may compromise patient outcomes and promote the emergence of bacterial resistance...
April 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28396542/ethambutol-is-cleared-by-a-contemporary-high-flux-hemodialyzer-and-drug-monitoring-ensures-safety-and-therapeuticity
#11
Rusheng Chew, Sarah Jongbloed, Dev Jegatheesan, Helen Healy, Kim Ta, Jacobus Ungerer, Brett McWhinney, Peter Donovan, Marion L Woods
It is uncertain, given the lack of recent data and the inconclusive nature of previous data, whether ethambutol is cleared by hemodialysis using contemporary dialyzers. We measured serum ethambutol concentrations before, during and one hour after hemodialysis in a 75-year-old Caucasian male receiving ethambutol for disseminated Bacille Calmette-Guérin infection. There was a mean 41% decrease in serum ethambutol concentration during dialysis, confirming the hemodialyzability of ethambutol and the utility of drug monitoring in ensuring safety...
April 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28385545/current-in-vitro-methods-to-determine-hepatic-kpuu-a-comparison-of-their-usefulness-and-limitations
#12
Julia Riede, Gian Camenisch, Jörg Huwyler, Birk Poller
Unbound intrahepatic drug concentrations determine the interaction potential with intracellular targets related to toxicity, pharmacokinetics or pharmacodynamics. Recently, the unbound liver-to-blood partition coefficient (Kpuu) based on the Extended Clearance Model (ECM) has been developed providing indirect estimates of unbound intrahepatic drug concentrations. This study aimed to determine Kpuu for 18 diverse drug compounds by three alternative in vitro methods and to compare the outcome with the ECM approach...
April 3, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28383717/characteristics-and-early-clinical-outcomes-of-patients-undergoing-totally-subcutaneous-vs-transvenous-single-chamber-implantable-cardioverter-defibrillator-placement
#13
Ali A Mithani, Heaton Kath, Krystal Hunter, John Andriulli, Matthew Ortman, Julie Field, Andrea M Russo
Aims: In 2012, the first totally Subcutaneous Implantable Cardioverter-Defibrillator (S-ICD) was approved by the Food and Drug Administration (FDA) in the United States. A possible benefit of this device is that it does not involve placing leads 'in' or 'on' the heart, potentially reducing complications. Methods amd results: Ninety-one S-ICD and 182 single chamber TV-ICD implants were performed between 10/22/2012 and 9/22/2015. During this period of time, 91 patients with S-ICD were matched to TV-ICD patients using single centre NCDR ICD Registry Data based on dialysis status, gender, and age...
April 4, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28381773/a-novel-chemical-enhancer-approach-for-transdermal-drug-delivery-with-c17-monoglycerol-ester-liquid-crystal-forming-lipid
#14
Wesam R Kadhum, Shohei Sekiguchi, Ichiro Hijikuro, Hiroaki Todo, Kenji Sugibayashi
Transdermal administration of drugs represents an excellent alternative to conventional pharmaceutical dosage forms. However, insufficient penetration of the active pharmaceutical substance through the skin is a common problem. Thus, in the present study we evaluated the skin permeation enhancing ability of liquid crystal (LC) topical formulations. A recently developed LC-forming lipid, C17-monoglycerol ester (MGE), was evaluated and compared with glycerol monoolate (GMO), which is considered as the gold standard for LC formulations...
April 4, 2017: Journal of Oleo Science
https://www.readbyqxmd.com/read/28376038/elbasvir-grazoprevir-use-in-postliver-transplantation-patients-on-hemodialysis
#15
Michelle T Martin, Sean Koppe
BACKGROUND: Current national hepatitis C virus (HCV) guidelines do not recommend the use of elbasvir/grazoprevir (EBR/GZR) in postliver transplantation (LT) patients due to drug-drug interactions (DDIs) with immunosuppression agents. However, recommendations do not address the treatment of HCV in renally-impaired post-LT patients. Treatment regimens that are recommended for post-LT patients are not safe in patients with severe renal impairment and patients on dialysis. EBR/GZR is approved for use in patients with renal impairment and patients on dialysis, but not in the post-LT setting...
April 3, 2017: Transplantation
https://www.readbyqxmd.com/read/28371161/ferric-pyrophosphate-citrate-as-an-iron-replacement-agent-for-patients-receiving-hemodialysis
#16
Steven Fishbane, Hitesh H Shah
Treatment of anemia remains an integral component in the care of patients with end stage kidney disease receiving dialysis. Currently, both erythropoiesis stimulating agents and iron replacement agents remain important anemia management strategies for patients undergoing hemodialysis (HD). Ferric pyrophosphate citrate (FPC) was approved by the U.S. Food and Drug Administration in January 2015 as an iron replacement product in adult patients receiving long-term maintenance HD. FPC is administered to patients on HD through the dialysate...
April 3, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28366609/no-evidence-of-increased-ocular-involvement-in-candidemic-patients-initially-treated-with-echinocandins
#17
P Muñoz, A Vena, B Padilla, M Valerio, M I Sanchez, M Puig-Asensio, J Fortún, M Fernández-Ruiz, P Merino, J E Losa, A Loza, R A Rivas, E Bouza
Candins are commonly used as initial therapy in patients with candidemia and are known to diffuse poorly into ocular tissue. The aim of our multicenter study was to assess whether eye involvement was more common in patients initially treated with echinocandins. We performed a post hoc analysis of a prospective, multicenter, population-based candidemic surveillance program implemented in Spain during 2010-2011 (CANDIPOP project). Eye involvement was detected in 13 of 168 patients with candidemia (7.7%) who underwent ophthalmoscopy...
February 27, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28365514/automation-of-plasma-protein-binding-assay-using-rapid-equilibrium-dialysis-device-and-tecan-workstation
#18
Zhengqi Ye, Craig Zetterberg, Hong Gao
Binding of drug molecules to plasma proteins is an important parameter in assessing drug ADME properties. Plasma protein binding (PPB) assays are routinely performed during drug discovery and development. A fully automated PPB assay was developed using rapid equilibrium dialysis (RED) device and Tecan workstation coupled to an automated incubator. The PPB assay was carried out in unsealed RED plates which allowed the assay to be fully automated. The plasma pH was maintained at 7.4 during the 6-h dialysis under 2% CO2 condition...
June 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28360466/rare-cause-of-paradoxical-worsening-of-pleural-effusion-in-a-patient-with-tuberculosis
#19
Paramasivan Duraikannan, S Saheer, T Balamugesh, D J Christopher
A 33-year-old patient, Known case of chronic kidney disease on maintenance dialysis presented with complaints of low-grade fever and weight loss of 2 months duration. Computed tomography (CT) revealed bilateral mild pleural effusion with significant mediastinal and abdominal adenopathy. CT-guided fine-needle aspiration cytology of abdominal lymph nodes and bone marrow culture was suggestive of tuberculosis. The patient was started on four drug anti-tubercular therapy, post 6 weeks of initiation he developed new onset fever and chest X-ray revealed moderate right pleural effusion...
March 2017: Lung India: Official Organ of Indian Chest Society
https://www.readbyqxmd.com/read/28356738/ph-sensitive-micelles-self-assembled-from-polymer-brush-pae-g-cholesterol-b-peg-b-pae-g-cholesterol-for-anticancer-drug-delivery-and-controlled-release
#20
Xiangxuan Huang, Wenbo Liao, Gang Zhang, Shimin Kang, Can Yang Zhang
A novel amphiphilic pH-sensitive triblock polymer brush (poly(β-amino esters)-g-cholesterol)-b-poly(ethylene glycol)-b-(poly(β-amino esters)-g-cholesterol) ((PAE-g-Chol)-b-PEG-b-(PAE-g-Chol)) was designed and synthesized successfully through a three-step reaction, and their self-assembled polymeric micelles were used as hydrophobic anticancer drug delivery carriers to realize effectively controlled release. The critical micelle concentrations were 6.8 μg/mL, 12.6 μg/mL, 17.4 μg/mL, and 26.6 μg/mL at pH values of 7...
2017: International Journal of Nanomedicine
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