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Renal clearance

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https://www.readbyqxmd.com/read/28444760/vancomycin-levels-are-frequently-subtherapeutic-in-critically-ill-patients-a-prospective-observational-study
#1
V Bakke, H Sporsem, E Von der Lippe, I Nordøy, Y Lao, H C Nyrerød, L Sandvik, K R Hårvig, J F Bugge, E Helset
BACKGROUND: Appropriate utilization of vancomycin is important to attain therapeutic targets while avoiding clinical failure and the development of antimicrobial resistance. Our aim was to observe the use of vancomycin in an intensive care population, with the main focus on achievement of therapeutic serum concentrations (15-20 mg/l) and to evaluate how this was influenced by dose regimens, use of guidelines and therapeutic drug monitoring. METHODS: A prospective observational study was carried out in the intensive care units at two tertiary hospitals in Norway...
April 25, 2017: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/28442904/anti-fgfr1-aptamer-tagged-superparamagnetic-conjugates-for-anticancer-hyperthermia-therapy
#2
Przemysław M Jurek, Konrad Zabłocki, Urszula Waśko, Maciej P Mazurek, Jacek Otlewski, Filip Jeleń
Compounds that recognize and strongly bind to molecular targets are one of the cornerstones of modern pharmaceutics. Work has been ongoing for the past 25 years on the therapeutic use of aptamers, nucleic acid molecules, whose three-dimensional structure is the result of interactions between complementary base pairs. The aptamers selection methods allow the oligonucleotides which bind the molecular target in its native environment to be quickly isolated from a large library of random oligonucleotides. The possibilities presented for aptamers in the field of targeted therapy require the application of effective carriers to counter the renal clearance effect and/or functional cargo to exert therapeutic action if the aptamer is only used as a targeting moiety...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28442499/absorption-distribution-metabolism-and-excretion-of-the-oral-prostaglandin-d2-receptor-2-dp2-antagonist-fevipiprant-qaw039-in-healthy-volunteers-and-in-vitro
#3
David Pearson, H Markus Weiss, Yi Jin, Jan Jaap van Lier, Veit J Erpenbeck, Ulrike Glaenzel, Peter End, Ralph Woessner, Fabian Eggimann, Gian Camenisch
Fevipiprant is a novel oral prostaglandin D2 receptor 2 (DP2; also known as CRTh2) antagonist, which is currently in development for the treatment of severe asthma and atopic dermatitis. We investigated the absorption, distribution, metabolism, and excretion properties of fevipiprant in healthy subjects after a single 200 mg oral dose of [(14)C]-radiolabeled fevipiprant. Fevipiprant and metabolites were analyzed by liquid chromatography coupled to tandem mass spectrometry and radioactivity measurements, and mechanistic in vitro studies were performed to investigate clearance pathways and covalent plasma protein binding...
April 25, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28439441/comparison-of-effects-of-low-flow-sevoflurane-and-low-flow-desflurane-anaesthesia-on-renal-functions-using-cystatin-c
#4
Gökçen Duymaz, Seyhan Yağar, Ayşegül Özgök
OBJECTIVE: Numerous studies have indicated nephrotoxic effects of sevoflurane because of its two bioproducts compound A and fluoride. Cystatin C (CyC) is a more sensitive biomarker than creatinine to show early and mild changes in kidney function. We designed this prospective randomised study to compare the effects of low-flow sevoflurane anaesthesia and low-flow desflurane anaesthesia on renal functions based on CyC levels. No studies have evaluated the effects of low-flow sevoflurane anaesthesia on renal functions based on CyC levels to date...
April 2017: Turkish Journal of Anaesthesiology and Reanimation
https://www.readbyqxmd.com/read/28437851/fexofenadine-a-putative-in-vivo-p-glycoprotein-probe-fails-to-predict-clearance-of-the-substrate-tacrolimus-in-renal-recipients
#5
Thomas Vanhove, Thomas Bouillon, Henriëtte de Loor, Pieter Annaert, Dirk R J Kuypers
Whether combined use of probe drugs for CYP3A4 and P-glycoprotein can clarify the relative contribution of these proteins to pharmacokinetic variability of a dual substrate like tacrolimus has never been assessed. Seventy renal recipients underwent simultaneous 8-hour pharmacokinetic profiles for tacrolimus, the CYP3A4 probe midazolam and the putative P-glycoprotein probe fexofenadine. Patients were genotyped for polymorphisms in CYP3A5, CYP3A4, ABCB1, ABCC2 and SLCO2B1, -1B1 and 1B3. Carriers of the ABCB1 2677G>A polymorphism displayed lower fexofenadine Cmax (-66%; P=0...
April 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28436712/disposition-and-metabolism-of-14-c-galunisertib-a-tgf-%C3%AE-ri-kinase-alk5-inhibitor-following-oral-administration-in-healthy-subjects-and-mechanistic-prediction-of-the-effect-of-itraconazole-on-galunisertib-pharmacokinetics
#6
Kenneth C Cassidy, Ivelina Gueorguieva, Colin Miles, Jessica Rehmel, Ping Yi, William J Ehlhardt
The disposition and metabolism of galunisertib (LY2157299 monohydrate, a TGF-βRI Kinase/ALK5 Inhibitor) was characterized following a single oral dose of 150 mg of [(14)C]-galunisertib (100 µCi) to six healthy human subjects. The galunisertib plasma half-life was 8.6 h, while the (14)C half-life was 10.0 h. Galunisertib was abundant in circulation (40.3% of the (14)C AUC0-24h), with 7 additional metabolites detected in plasma. Two metabolites LSN3199597 (M5, mono-oxidation), and M4 (glucuronide of M3) were the most abundant circulating metabolites (10...
April 24, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28434550/renal-failure-after-cardiac-operations-not-all-acute-kidney-injury-is-the-same
#7
Todd C Crawford, J Trent Magruder, Joshua C Grimm, Shin-Rong Lee, Alejandro Suarez-Pierre, David Lehenbauer, Christopher M Sciortino, Robert S Higgins, Duke E Cameron, John V Conte, Glenn J Whitman
BACKGROUND: The Society of Thoracic Surgeons (STS) database does not distinguish between a decline in creatinine clearance vs new hemodialysis (HD) when qualifying acute renal failure (ARF) after a cardiac operation. We hypothesized that patients requiring HD experience significantly greater postoperative morbidity and death. METHODS: We included all patients who underwent STS index cardiac operations at our institution from 2008 to March 2015 and did not have preexisting renal failure (creatinine >4...
April 20, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28434125/kidney-morphological-parameters-measured-using-noncontrast-enhanced-steady-state-free-precession-mri-with-spatially-selective-inversion-recovery-pulse-correlate-with-egfr-in-patients-with-advanced-ckd
#8
Tadashi Otsuka, Yoshikatsu Kaneko, Yuya Sato, Ryohei Kaseda, Ryuji Aoyagi, Suguru Yamamoto, Shin Goto, Ichiei Narita
BACKGROUND: It is well known that atrophic renal changes are associated with chronic kidney disease (CKD) progression, but conventional diagnostic imaging methods such as noncontrast-enhanced computed tomography and magnetic resonance imaging (MRI) have been insufficient for precisely assessing kidney function because they cannot clearly distinguish between the medulla and cortex. Hence, here we used noncontrast-enhanced steady-state free precession (SSFP) MRI with a spatially selective inversion recovery (IR) pulse to improve visibility for renal corticomedullary differentiation and evaluated the association between morphological parameters and kidney function in patients with CKD...
April 22, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28432550/estradiol-mitigates-ischemia-reperfusion-induced-acute-renal-failure-through-nmda-receptor-antagonism-in-rats
#9
Amrit Pal Singh, Nirmal Singh, Preet Mohinder Singh Bedi
In the present study, we investigated possible involvement of N-methyl-D-aspartate receptors (NMDAR) in estradiol mediated protection against ischemia reperfusion (I/R)-induced acute renal failure (ARF) in rats. Bilateral renal ischemia of 40 min followed by reperfusion for 24 h induced ARF in male wistar rats. Quantification of serum creatinine, creatinine clearance (CrCl), blood urea nitrogen (BUN), uric acid, potassium, fractional excretion of sodium (FeNa), and urinary microproteins was done to assess I/R-induced renal damage in rats...
April 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28429121/renovascular-hypertension-results-in-adulthood-of-renal-autotransplantation-performed-in-children
#10
Bertrand Chavent, Ambroise Duprey, Marie-Pierre Lavocat, Christine Fichtner, Anne-Marie Beraud, Jean-Noel Albertini, Jean-Pierre Favre, Nicolas Maillard, Xavier Barral
BACKGROUND: This study describes the long-term results of renal autotransplantation for renovascular hypertension performed in children who are now 21 years of age or older. METHODS: Sixteen children (4 boys, 12 girls) with a mean age of 11.2 years at the time of the procedure underwent ex-vivo surgery at the university hospital of Saint-Etienne between 1992 and 2008. Acetylsalicylic acid was used for antiplatelet therapy in the postoperative period, without routine anticoagulation...
April 20, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28428365/interaction-and-transport-of-methamphetamine-and-its-primary-metabolites-by-organic-cation-and-multidrug-and-toxin-extrusion-transporters
#11
David J Wagner, Jennifer E Sager, Haichuan Duan, Nina Isoherranen, Joanne Wang
Methamphetamine is one of the most abused illicit drugs with roughly 1.2 million users in the United States alone. A large portion of methamphetamine and its metabolites is eliminated by the kidney with renal clearance larger than glomerular filtration clearance. Yet the mechanism of active renal secretion is poorly understood. The goals of this study were to characterize the interaction of methamphetamine and its major metabolites with organic cation transporters (OCT) and multidrug and toxin extrusion (MATE) transporters and to identify the major transporters involved in the disposition of methamphetamine and its major metabolites, amphetamine and p-hydroxymethamphetamine (p-OHMA)...
April 20, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28426831/representation-and-reporting-of-kidney-disease-in-cerebrovascular-disease-a-systematic-review-of-randomized-controlled-trials
#12
Ioannis Konstantinidis, Shanti Patel, Marianne Camargo, Achint Patel, Priti Poojary, Steven G Coca, Girish N Nadkarni
Patients with kidney disease (KD) are at increased risk for cerebrovascular disease (CVD) and CVD patients with KD have worse outcomes. We aimed to determine the representation of KD patients in major randomized controlled trials (RCTs) of CVD interventions. We searched MEDLINE for reports of major CVD trials published through February 9, 2017. We excluded trials that did not report mortality outcomes, enrolled fewer than 100 participants, or were subgroup, follow-up, or post-hoc analyses. Two independent reviewers performed study selection and data extraction...
2017: PloS One
https://www.readbyqxmd.com/read/28419522/a-general-empirical-model-for-renal-drug-handling-in-pharmacokinetic-analyses
#13
Daniel F B Wright, Stephen B Duffull
Dose adjustment in renal insufficiency is generally based on the assumption that renal drug clearance is related linearly to glomerular filtration rate. The theory underpinning this model is the Intact Nephron Hypothesis, where impaired renal function is said to be caused by a reduction in the number of complete (intact) nephrons. The purpose of this commentary is to propose a general empirical model for renal drug handling. We will explore models for renal function under two scenarios; one that aligns with the intact nephron hypothesis, and one that relaxes the assumptions of this hypothesis...
April 16, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28419483/pharmacokinetic-study-of-intravenous-acetaminophen-administered-to-critically-ill-multiple-trauma-patients-at-the-usual-dosage-and-a-new-proposal-for-administration
#14
Oscar Fuster-Lluch, Pedro Zapater-Hernández, Manuel Gerónimo-Pardo
The pharmacokinetic profile of intravenous acetaminophen administered to critically ill multiple-trauma patients was studied after 4 consecutive doses of 1 g every 6 hours. Eleven blood samples were taken (predose and 15, 30, 45, 60, 90, 120, 180, 240, 300, and 360 minutes postdose), and urine was collected (during 6-hour intervals between doses) to determine serum and urine acetaminophen concentrations. These were used to calculate the following pharmacokinetic parameters: maximum and minimum concentrations, terminal half-life, area under serum concentration-time curve from 0 to 6 hours, mean residence time, volume of distribution, and serum and renal clearance of acetaminophen...
April 17, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28417217/levels-of-cystatin-c-in-low-and-high-flux-hemodialysis-in-children-with-end-stage-renal-disease
#15
Fatina I Fadel, Abbass A Mourad, Azza M O Abdel Rahman, Hafez M Bazaraa, Mohamed Farouk Mohamed, Dalia H El-Lebedy, Mohamed M Soliman
BACKGROUND: Cystatin-C (CyC) is a middle molecule that is freely filtered at the glomerulus and almost completely reabsorbed by the proximal tubules. The aim of this study was to evaluate serum CyC and its reduction ratio as a biomarker for assessing the adequacy of the hemodialysis (HD) sessions in children with end-stage renal disease on maintenance HD. We also compared levels of CyC in patients on low-flux HD (LFH) and high-flux HD (HFH). METHODS: Forty patients were included in the study and divided into two groups, with one group (16 patients) receiving HFH and the other group receiving LFH (24 patients) (high-flux and low-flux polysulfone filters, respectively)...
April 17, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28417195/rrx-001-protects-against-cisplatin-induced-toxicities
#16
Bryan Oronsky, Tony R Reid, Christopher Larson, Corey A Carter, Christina E Brzezniak, Arnold Oronsky, Pedro Cabrales
PURPOSE: RRx-001, a minimally toxic tumor-associated macrophage and neutrophil-repolarizing agent, is under investigation in Phase II clinical trials as a sensitizer/resensitizer to cisplatin and carboplatin. On the basis of anecdotal clinical observations of improved platinum tolerability following a priming period with RRx-001 as well as preclinical studies that have previously demonstrated radioprotection of intestinal stem cells and cardioprotection from doxorubicin, the in vivo cytoprotective potential of RRx-001 pretreatment against cisplatin-induced bone marrow suppression and renal toxicity was investigated...
April 17, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28416419/evaluation-of-renal-transporter-inhibition-employing-creatinine-as-a-substrate-in-vitro-to-assess-the-clinical-risk-of-elevated-serum-creatinine
#17
Sumathy Mathialagan, A David Rodrigues, Bo Feng
Creatinine is a widely accepted biomarker for renal toxicity, but its renal clearance via transporter-mediated active secretion is significant. For a given new chemical entity, therefore, elevations in serum creatinine (SCr) can be caused by the inhibition of one or more renal transporters without renal toxicity. In the present study, an effort was made to assess the correlation between the inhibition of renal transporters in vitro and elevations in SCr. A total of 15 compounds were chosen based on their known effect on SCr and minimal impact on glomerular filtration rate...
April 14, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28416145/the-ginkgo-biloba-extract-gbe-protects-the-kidney-from-damage-produced-by-a-single-and-low-dose-of-carbon-tetrachloride-in-adult-male-rats
#18
R M Chávez-Morales, F Jaramillo-Juárez, M L Rodríguez-Vázquez, M C Martínez-Saldaña, F A Posadas Del Río, J A Garfias-López
Gingko biloba leaves have been used as herbal medicine in China for 5000 years, and the standardized leaf extract (GB-STE) has some beneficial effects in the treatment of age-related, cardiovascular, and neurological diseases. The aim of this study was to investigate the renoprotective effects of the Gingko biloba extract (GbE) against the toxicity of a single and relatively low dose of carbon tetrachloride (CCl4). In male adult Wistar rats, we determined the urine flux, the concentration of total proteins in urine, the concentration of glucose in urine, and the concentration of malondialdehyde (MDA) in renal cortex as well as two markers of renal function (clearance of inulin and p-aminohippurate); we also compared the histological lesions caused by CCl4...
April 13, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28414302/increased-salt-consumption-induces-body-water-conservation-and-decreases-fluid-intake
#19
Natalia Rakova, Kento Kitada, Kathrin Lerchl, Anke Dahlmann, Anna Birukov, Steffen Daub, Christoph Kopp, Tetyana Pedchenko, Yahua Zhang, Luis Beck, Bernd Johannes, Adriana Marton, Dominik N Müller, Manfred Rauh, Friedrich C Luft, Jens Titze
BACKGROUND: The idea that increasing salt intake increases drinking and urine volume is widely accepted. We tested the hypothesis that an increase in salt intake of 6 g/d would change fluid balance in men living under ultra-long-term controlled conditions. METHODS: Over the course of 2 separate space flight simulation studies of 105 and 205 days' duration, we exposed 10 healthy men to 3 salt intake levels (12, 9, or 6 g/d). All other nutrients were maintained constant...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28413323/preventive-effect-of-fermented-black-ginseng-against-cisplatin-induced-nephrotoxicity-in-rats
#20
Kiwon Jung, Jun Min An, Dae-Woon Eom, Ki Sung Kang, Su-Nam Kim
BACKGROUND: Fermented black ginseng (FBG) is processed ginseng by the repeated heat treatment and fermentation of raw ginseng. The protective effect and mechanism of FBG on cisplatin-induced nephrotoxicity was investigated to evaluate its therapeutic potential. METHODS: The free radical scavenging activity of FBG was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH). In addition, the protective effect against cisplatin-induced renal damage was tested in rats. FBG was orally administered every day at a dose of 150 mg/kg body weight for 10 d, and a single dose of cisplatin was administered intraperitoneally (7...
April 2017: Journal of Ginseng Research
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