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drug dosing in renal disease

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https://www.readbyqxmd.com/read/29791023/comparison-of-the-cockcroft-gault-mdrd-and-ckd-epi-equations-for-estimating-ganciclovir-clearance
#1
Maria-Eugenia Palacio-Lacambra, Immaculada Comas-Reixach, Albert Blanco-Grau, Josep-Maria Suñé-Negre, Alfonso Segarra-Medrano, José-Bruno Montoro-Ronsano
BACKGROUND: Accurately estimating kidney function is essential for the safe administration of renally cleared drugs like ganciclovir. Current practice recommends adjusting renally eliminated drugs according to the Cockcroft-Gault equation. There is no data on the utility of the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in ganciclovir dosing. PURPOSE: To evaluate which renal function equation best predicts ganciclovir clearance...
May 23, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29786782/preclinical-impact-of-high-dose-intermittent-antiangiogenic-tyrosine-kinase-inhibitor-pazopanib-in-intrinsically-resistant-tumor-models
#2
Elaine Reguera-Nuñez, Shan Man, Ping Xu, Robert S Kerbel
Antiangiogenic tyrosine kinase inhibitors (TKIs) target vascular endothelial growth factor receptors and other receptor tyrosine kinases. As a result of toxicity, the clinical failures or the modest benefits associated with antiangiogenic TKI therapy may be related in some cases to suboptimal drug dosing and scheduling, thereby facilitating resistance. Most antiangiogenic TKIs, including pazopanib, are administered on a continuous daily basis. Here, instead, we evaluated the impact of increasing the dose and administering the drug intermittently...
May 21, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29766465/effects-of-fenoldopam-on-renal-blood-flow-in-hypertensive-chronic-kidney-disease
#3
Valentina Rovella, Michele Ferrannini, Manfredi Tesauro, Giulia Marrone, Andrea Busca, Roberto Sorge, Simone Manca di Villahermosa, Maurizio Casasco, Nicola Di Daniele, Annalisa Noce
BACKGROUND AND AIM: The synthetic drug fenoldopam mesylate (FM) may have a renoprotective role, and a "renal dose" of 0.1 µg/kg/min intravenous (IV) infusion of FM has been reported as able to increase renal blood flow without affecting systemic blood pressure. But conclusive data are still lacking. We aimed to investigate by color-Doppler ultrasonography the effects of IV administration of FM at this dosage in hypertensive chronic kidney disease (CKD) patients, and verify whether it may induce any systemic hemodynamic alteration...
May 15, 2018: Journal of Nephrology
https://www.readbyqxmd.com/read/29764549/-clinical-verification-of-vancomycin-population-pharmacokinetics-in-patients-with-augmented-renal-clearance
#4
Haodi Lu, Lian Tang, Shengmin Xue, Zhiwei Zhuang, Jie Fang, Fuli Zhao, Erning Shang
OBJECTIVE: To evaluate the predictive value and to verify the clinical effect of JPKD-vancomycin for the trough concentration of vancomycin in patients with augmented renal clearance (ARC), and to provide a reference for clinical individualized drug therapy. METHODS: A retrospective analysis was conducted. The clinical data of 48 adult patients with ARC using vancomycin and monitoring steady-state trough concentration of vancomycin admitted to Suzhou Hospital Affiliated to Nanjing Medical University from July 2013 to July 2017 were collected...
May 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/29761242/safety-and-efficacy-of-benzbromarone-and-febuxostat-in-hyperuricemia-patients-with-chronic-kidney-disease-a-prospective-pilot-study
#5
Haibo Yu, Xinying Liu, Yaxiang Song, Jiafen Cheng, Hui Bao, Ling Qin, Xuan Zhou, Ling Wang, Ai Peng
BACKGROUND: To compare the safety and efficacy of benzbromarone and febuxostat in hyperuricemia patients with estimated glomerular filtration rate (eGFR) 20-60 mL/min/1.73 m2 . METHODS: This study was a single-centered, parallel-grouped, randomized clinical trial (RCT). We randomly assigned hyperuricemia participants with eGFR 20-60 mL/min/1.73 m2 into benzbromarone and febuxostat treatment group. Drugs were adjusted by titration from small doses. RESULTS: Seventy-three eligible participants enrolled, 66 subjects (33 in each group) were included finally for analysis...
May 14, 2018: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29748012/a-phase-i-study-of-nintedanib-combined-with-cisplatin-gemcitabine-as-first-line-therapy-for-advanced-squamous-non-small-cell-lung-cancer-lume-lung-3
#6
Martin Forster, Allan Hackshaw, Tommaso De Pas, Manuel Cobo, Pilar Garrido, Yvonne Summers, Anne-Marie C Dingemans, Michael Flynn, David Schnell, Ute von Wangenheim, Arsene-Bienvenu Loembé, Rolf Kaiser, Siow Ming Lee
BACKGROUND: There are limited treatment options for squamous non-small cell lung cancer (sqNSCLC) and prognosis remains poor. The safety and pharmacokinetics (PK) of nintedanib, a triple angiokinase inhibitor, plus cisplatin/gemcitabine as first-line treatment for advanced sqNSCLC patients, were evaluated. MATERIALS AND METHODS: A phase I, dose-escalation study administering drugs in a 21-day cycle: cisplatin (75 mg/m2 , Day 1), gemcitabine (1250 mg/m2 , Days 1 and 8) and nintedanib (Days 2-7, 9-21) were given for 4-6 cycles, followed by monotherapy until disease progression or adverse events (AEs)...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29738375/magnesium-citrate-protects-against-vascular-calcification-in-an-adenine-induced-crf-rat-model
#7
PhD Zhihui-Yao, M D Yang-Xu, M D Weidong-Ma, Xin-Yuan Sun, PhD Shan-Jia, M D Yang-Zheng, M D Xiaohuan-Liu, M D Yajie-Fan, M D Congxia-Wang
BACKGROUND: Hypomagnemia was identified as a strong risk factor for cardiovascular disease in patients with chronic renal failure (CRF). However, the effects of magnesium (Mg) on vascular calcification (VC) have not been fully elucidated. Thus we aim to determine the effects of Mg citrate (MgCit) on VC in CRF rats. METHODS: Rats were divided into 5 groups: group 1 (normal diet); group 2 (normal diet with MgCit); group 3 (VC model of CRF induced by 0.75% adenine and 0...
April 24, 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29731610/treatment-adherence-among-adult-hypertensive-patients-a-cross-sectional-retrospective-study-in-primary-care-in-romania
#8
Ioan Tilea, Dorina Petra, Septimiu Voidazan, Elena Ardeleanu, Andreea Varga
Purpose: This study was performed to elucidate the level of adherence to antihypertensive treatment in adult subjects attending a family medicine clinic in a city in central Romania. Patients and methods: A cross-sectional, retrospective study was performed on a cohort of hypertensive adults. A total of 525 participants were selected from 1,714 adults attending a single urban family medicine practice. Assessment of adherence to therapy was performed by a chart review of prescription and clinical records over a 4-year study period...
2018: Patient Preference and Adherence
https://www.readbyqxmd.com/read/29716795/metformin-prevents-the-development-of-severe-chronic-kidney-disease-and-its-associated-mineral-and-bone-disorder
#9
Ellen Neven, Benjamin Vervaet, Kerstin Brand, Ulrike Gottwald-Hostalek, Britt Opdebeeck, Annelies De Maré, Anja Verhulst, Jean-Daniel Lalau, Said Kamel, Marc E De Broe, Patrick C D'Haese
Chronic kidney disease (CKD) causes dysregulation of mineral metabolism, vascular calcification and renal osteodystrophy, an entity called 'CKD-Mineral and Bone Disorder' (CKD-MBD). Here we determine whether metformin, an anti-diabetic drug, exerts favorable effects on progressive, severe CKD and concomitant mineral metabolism disturbances. Rats with CKD-MBD, induced by a 0.25% adenine diet for eight weeks, were treated with 200 mg/kg/day metformin or vehicle from one week after CKD induction onward. Severe, stable CKD along with marked hyperphosphatemia and hypocalcemia developed in these rats which led to arterial calcification and high bone turnover disease...
April 28, 2018: Kidney International
https://www.readbyqxmd.com/read/29700792/preventive-effect-of-shenkang-injection-against-high-glucose-induced-senescence-of-renal-tubular-cells
#10
Biqiong Fu, Jie Yang, Jia Chen, Lirong Lin, Kehong Chen, Weiwei Zhang, Jianguo Zhang, Yani He
Shenkang injection (SKI) is a classic prescription composed of Radix Astragali, rhubarb, Astragalus, Safflower, and Salvia. This treatment was approved by the State Food and Drug Administration of China in 1999 for treatment of chronic kidney diseases based on good efficacy and safety. This study aimed to investigate the protective effect of SKI against high glucose (HG)-induced renal tubular cell senescence and its underlying mechanism. Primary renal proximal tubule epithelial cells were cultured in (1) control medium (control group), medium containing 5 mmol/L glucose; (2) mannitol medium (mannitol group), medium containing 5 mmol/L glucose, and 25 mmol/L mannitol; (3) HG medium (HG group) containing 30 mmol/L glucose; (4) SKI treatment at high (200 mg/L), medium (100 mg/L), or low (50 mg/L) concentration in HG medium (HG + SKI group); or (5) 200 mg/L SKI treatment in control medium (control + SKI group) for 72 h...
April 25, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29690924/the-effect-of-regularly-dosed-paracetamol-versus-no-paracetamol-on-renal-function-in-plasmodium-knowlesi-malaria-packnow-study-protocol-for-a-randomised-controlled-trial
#11
Daniel J Cooper, Katherine Plewes, Matthew J Grigg, Giri S Rajahram, Kim A Piera, Timothy William, Mark D Chatfield, Tsin Wen Yeo, Arjen M Dondorp, Nicholas M Anstey, Bridget E Barber
BACKGROUND: Plasmodium knowlesi is the most common cause of human malaria in Malaysia. Acute kidney injury (AKI) is a frequent complication. AKI of any cause can have long-term consequences, including increased risk of chronic kidney disease, adverse cardiovascular events and increased mortality. Additional management strategies are therefore needed to reduce the frequency and severity of AKI in malaria. In falciparum malaria, cell-free haemoglobin (CFHb)-mediated oxidative damage contributes to AKI...
April 24, 2018: Trials
https://www.readbyqxmd.com/read/29682773/mortality-data-from-the-european-adrenal-insufficiency-registry-patient-characterization-and-associations
#12
Marcus Quinkler, Bertil Ekman, Pinggao Zhang, Andrea M Isidori, Robert D Murray
OBJECTIVE: Mortality from primary and secondary adrenal insufficiency (AI; PAI and SAI, respectively) is 2-3-fold higher than in the general population. Mortality relates to cardiovascular disease, acute adrenal crisis (AC), cancer and infections; however, there has been little further characterization of patients who have died. DESIGN/METHODS: We analysed real-world data from 2034 patients (801 PAI, 1233 SAI) in the European Adrenal Insufficiency Registry (EU-AIR; NCT01661387)...
April 22, 2018: Clinical Endocrinology
https://www.readbyqxmd.com/read/29669701/crizotinib-in-patients-with-advanced-inoperable-inflammatory-myofibroblastic-tumours-with-and-without-anaplastic-lymphoma-kinase-gene-alterations-european-organisation-for-research-and-treatment-of-cancer-90101-create-a-multicentre-single-drug-prospective-non
#13
Patrick Schöffski, Jozef Sufliarsky, Hans Gelderblom, Jean-Yves Blay, Sandra J Strauss, Silvia Stacchiotti, Piotr Rutkowski, Lars H Lindner, Michael G Leahy, Antoine Italiano, Nicolas Isambert, Maria Debiec-Rychter, Raf Sciot, Thomas Van Cann, Sandrine Marréaud, Axelle Nzokirantevye, Sandra Collette, Agnieszka Wozniak
BACKGROUND: An inflammatory myofibroblastic tumour (IMFT) is a rare mesenchymal neoplasm characterised by anaplastic lymphoma kinase (ALK) gene rearrangements. We assessed the activity and safety of crizotinib, a tyrosine kinase inhibitor, targeting ALK in patients with advanced IMFT either with or without ALK alterations. METHODS: We did a multicentre, biomarker-driven, single-drug, non-randomised, open-label, two-stage phase 2 trial (European Organisation for Research and Treatment of Cancer 90101 CREATE) at 13 study sites (five university hospitals and eight specialty clinics) in eight European countries (Belgium, France, Germany, Italy, Netherlands, Poland, Slovakia, and the UK)...
April 12, 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29668485/prolonged-activity-and-toxicity-of-sirolimus-in-a-patient-with-metastatic-renal-perivascular-epithelioid-cell-tumor-a-case-report-and-literature-review
#14
Alessandra Raimondi, Francesca Colombo, Giulia Pintarelli, Carlo Morosi, Salvatore L Renne, Anna M Frezza, Maristella Saponara, Angelo P Dei Tos, Arabella Mazzocchi, Salvatore Provenzano, Paolo G Casali, Silvia Stacchiotti
Perivascular epithelioid cell tumor (PEComa) is a family of mesenchymal tumors. Conventional chemotherapy has little activity in this disease, but case reports are available on the activity of mammalian target of rapamycin inhibitors (e.g. sirolimus and temsirolimus). Pharmacokinetic assays of sirolimus are available as this drug has a precise therapeutic window and blood levels might be influenced by CYP3A4 polymorphisms and drug interactions. We report on a case of a patient with metastatic, progressive PEComa who started sirolimus at a dose of 5 mg/day with evidence of grade (G) 3 mucositis, G2 thrombocytopenia, and G1 leucopenia 10 days after the treatment started, in absence of concomitant medications or prohibited food assumption...
April 17, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29667038/complex-drug-drug-gene-disease-interactions-involving-cytochromes-p450-systematic-review-of-published-case-reports-and-clinical-perspectives
#15
REVIEW
Flavia Storelli, Caroline Samer, Jean-Luc Reny, Jules Desmeules, Youssef Daali
Drug pharmacokinetics (PK) is influenced by multiple intrinsic and extrinsic factors, among which concomitant medications are responsible for drug-drug interactions (DDIs) that may have a clinical relevance, resulting in adverse drug reactions or reduced efficacy. The addition of intrinsic factors affecting cytochromes P450 (CYPs) activity and/or expression, such as genetic polymorphisms and diseases, may potentiate the impact and clinical relevance of DDIs. In addition, greater variability in drug levels and exposures has been observed when such intrinsic factors are present in addition to concomitant medications perpetrating DDIs...
April 17, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29665445/acute-kidney-injury-during-treatment-with-high-dose-cloxacillin-a-report-of-23-cases-and-literature-review
#16
Aurélie Lavergne, Cécile Vigneau, Elisabeth Polard, Louise Triquet, Nathalie Rioux-Leclercq, Pierre Tattevin, Léonard Golbin
BACKGROUND: International guidelines recommend high-dose cloxacillin for endocarditis or osteoarticular infections due to meticillin-susceptible staphylococci. However, data on the tolerability of these regimens are scarce. METHODS: We used the computerized registry of suspected drug-related adverse events in our institution. Cases of acute kidney injury (AKI), as defined by KDIGO, in patients receiving high-dose cloxacillin, were retrospectively reviewed. Data were collected from medical charts on a standardized questionnaire...
April 14, 2018: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29643251/pharmacological-characterization-of-iw-1973-a-novel-soluble-guanylate-cyclase-stimulator-with-extensive-tissue-distribution-anti-hypertensive-anti-inflammatory-and-anti-fibrotic-effects-in-preclinical-models-of-disease
#17
Jenny V Tobin, Daniel P Zimmer, Courtney Shea, Peter Germano, Sylvie G Bernier, Guang Liu, Kim Long, Joy Miyashiro, Sheila Ranganath, Sarah Jacobson, Kim Tang, G-Yoon Jamie Im, James Sheppeck, Joel D Moore, Kristine Sykes, James Wakefield, Renee Sarno, Ali R Banijamali, Albert T Profy, G Todd Milne, Mark G Currie, Jaime L Masferrer
Soluble guanylate cyclase (sGC), a key signal-transduction enzyme, increases the conversion of guanosine-5'-triphosphate (GTP) to cyclic guanosine-3',5'-monophosphate (cGMP) upon binding of nitric oxide (NO). Endothelial dysfunction and/or reduced NO signaling have been implicated in cardiovascular disease pathogenesis and complications of diabetes, and have been associated with other disease states and aging. sGC stimulators are small-molecule drugs that bind sGC and enhance NO-mediated cGMP signaling. The pharmacological characterization of IW-1973, a novel clinical-stage sGC stimulator, is described...
April 11, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29625879/tivantinib-for-second-line-treatment-of-met-high-advanced-hepatocellular-carcinoma-metiv-hcc-a-final-analysis-of-a-phase-3-randomised-placebo-controlled-study
#18
Lorenza Rimassa, Eric Assenat, Markus Peck-Radosavljevic, Marc Pracht, Vittorina Zagonel, Philippe Mathurin, Elena Rota Caremoli, Camillo Porta, Bruno Daniele, Luigi Bolondi, Vincenzo Mazzaferro, William Harris, Nevena Damjanov, Davide Pastorelli, María Reig, Jennifer Knox, Francesca Negri, Jörg Trojan, Carlos López López, Nicola Personeni, Thomas Decaens, Marie Dupuy, Wolfgang Sieghart, Giovanni Abbadessa, Brian Schwartz, Maria Lamar, Terri Goldberg, Dale Shuster, Armando Santoro, Jordi Bruix
BACKGROUND: Tivantinib (ARQ 197), a selective, oral MET inhibitor, improved overall survival and progression-free survival compared with placebo in a randomised phase 2 study in patients with high MET expression (MET-high) hepatocellular carcinoma previously treated with sorafenib. The aim of this phase 3 study was to confirm the results of the phase 2 trial. METHODS: We did a phase 3, randomised, double-blind, placebo-controlled study in 90 centres in Australia, the Americas, Europe, and New Zealand...
April 3, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29610294/learned-immunosuppressive-placebo-responses-in-renal-transplant-patients
#19
Julia Kirchhof, Liubov Petrakova, Alexandra Brinkhoff, Sven Benson, Justine Schmidt, Maike Unteroberdörster, Benjamin Wilde, Ted J Kaptchuk, Oliver Witzke, Manfred Schedlowski
Patients after organ transplantation or with chronic, inflammatory autoimmune diseases require lifelong treatment with immunosuppressive drugs, which have toxic adverse effects. Recent insight into the neurobiology of placebo responses shows that associative conditioning procedures can be employed as placebo-induced dose reduction strategies in an immunopharmacological regimen. However, it is unclear whether learned immune responses can be produced in patient populations already receiving an immunosuppressive regimen...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29594677/monitoring-of-gentamicin-serum-concentrations-in-obstetrics-and-gynaecology-patients-in-namibia
#20
Bonifasius S Singu, Mwangana Mubita, Moses M Thikukutu, Josef K Mufenda, Shonag B McKenzie, Roger K Verbeeck
Background Therapeutic drug monitoring is frequently used to optimize the gentamicin dose. Objective The study investigated whether a 240 mg once daily standard dose achieves the recommended target serum gentamicin concentrations. Setting The prospective, observational study took place in the 2 major public hospitals in Namibia. Method Twenty-nine female patients receiving a standard dose (240 mg gentamicin once daily) participated in the study. Two blood samples were withdrawn to estimate gentamicin pharmacokinetic parameters...
March 28, 2018: International Journal of Clinical Pharmacy
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