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drug dosing in renal disease

Nathan R Unger, Marylee V Worley, Jamie J Kisgen, Elizabeth M Sherman, Lindsey M Childs-Kean
Current antiretrovirals (ARVs) have demonstrated the ability to prolong the life of an HIV infected individual via suppression of the virus and subsequent restoration of immune function. Despite significant advancement, there remains an opportunity for improvement. One ARV that attempts to fill global HIV therapeutic needs by balancing convenience, safety, and efficacy is elvitegravir (EVG). Areas covered: Using MEDLINE/PubMed, a literature search was conducted for published articles on the safety and efficacy of EVG in the treatment of HIV infection...
October 21, 2016: Expert Opinion on Pharmacotherapy
Verónica Poveda, Leonilde Amado, Madalena Filgueiras, Laetitia Teixeira, Vasco Miranda, Alice Santos-Silva, Constança Paúl, Elísio Costa
Non-adherence to medical plans is recognized as an important problem in dialysis patients, since it has been associated with increased morbidity and mortality, resulting in disproportionately high costs of care. The success of renal replacement therapy depends on the adherence of patients to the different aspects of the therapeutic strategy, which includes a complex drug regimen involving a wide variety of drugs and doses, several prescribed dialysis sessions with different durations, dietetic recommendations and restriction of fluid intake...
October 20, 2016: Renal Failure
Yuko Ohta, Azusa Ishizuka, Hisatomi Arima, Shinichiro Hayashi, Yoshio Iwashima, Masatsugu Kishida, Fumiki Yoshihara, Satoko Nakamura, Yuhei Kawano
Uric acid (UA) has been associated with hypertension, renal disease and cardiovascular disease. The aim of the present study was to compare the UA-lowering effects of a standard dose of the UA synthesis inhibitor febuxostat to a standard dose of the uricosuric agent benzbromarone, and to investigate the effects of a low-dose combination of both agents in hypertensive patients with hyperuricemia. Twenty hypertensive patients with inadequate UA control were administered febuxostat 40 mg (Feb), benzbromarone 50 mg (Ben) and febuxostat 20 mg and benzbromarone 25 mg (feb/ben) for 3 months each in a randomized modified crossover manner...
October 20, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
David John Webb
Treatment-resistant hypertension (TRH) is defined as the failure to achieve an office BP target of <140/90 mmHg (<130/80 mmHg in patients with chronic kidney disease (CKD) or diabetes) in patients with hypertension (HT), despite adherence to at least 3 antihypertensive medications at optimal tolerated doses, ideally including a diuretic (Calhoun et al., Circulation 2008). TRH identifies patients with hard-to-treat HT, who might benefit from specialist investigation and treatment. Although some studies put the prevalence of TRH as >10%, these levels may be inflated by white-coat hypertension and poor adherence...
September 2016: Journal of Hypertension
William C Cushman
Beginning with the Veterans Administration (VA) Cooperative Hypertension Study of the 1960 s, blood pressure (BP) lowering with antihypertensive medications has been shown to reduce major cardiovascular (CV) outcomes, including coronary heart disease, stroke, heart failure (HF) and CV and all-cause mortality in randomized controlled CV outcome trials. Multiple drugs were usually required in these trials to lower BP in treated participants. Medication regimens in the early trials, including the VA trial, included a thiazide-type diuretic (TTD) as initial therapy...
September 2016: Journal of Hypertension
George Bakris
Resistant hypertension is defined as a blood pressure above 140/90 mmHg despite adherence to a combination of at least three optimally dosed antihypertensive medications, one of which is a diuretic. Chronic kidney disease (CKD) is one of the more common patient comorbidities associated with resistant hypertension. Recommended low-salt diet and triple antihypertensive drug regimens that include a diuretic, should be complemented by the sequential addition of other antihypertensive drugs. CKD is associated with premature vascular ageing, characterized by accelerated arteriosclerosis or atherosclerosis and endothelial dysfunction...
September 2016: Journal of Hypertension
Kazuomi Kario
The essential benefit of the management of hypertension is derived from the blood pressure (BP) lowering per se, indicating the importance of BP throughout 24 hours. Recent guidelines stressed the importance of home BP for the diagnosis and management of hypertension. It is well-known that cardiovascular events occur more frequently in the morning BP levels have been shown to increase during the period from night to early morning. Clinical research using ambulatory BP monitoring (ABPM) or home BP monitoring has clarified that morning BP and BP surge are more closely related to the cardiovascular risk than office BP (Kario et al...
September 2016: Journal of Hypertension
Patrick Biggar, Frank Leistikow, Andreas Walper
AIMS: The aim of this study was to investigate the effectiveness, safety, and tolerability of iron isomaltoside in routine practical care of iron deficiency anemia (IDA) in patients with chronic renal failure. METHODS: The study included 698 patients with IDA on dialysis or with nondialysis chronic kidney disease (CKD) stages 3 - 5 designated by their physicians for treatment with iron isomaltoside. Data were recorded at baseline and after 3 and 9 months. Effectiveness data included measurement of hemoglobin (Hb), hematocrit, s-iron, transferrin saturation (TSAT), and s-ferritin...
October 14, 2016: Clinical Nephrology
Padmanee Sharma, Margaret K Callahan, Petri Bono, Joseph Kim, Pavlina Spiliopoulou, Emiliano Calvo, Rathi N Pillai, Patrick A Ott, Filippo de Braud, Michael Morse, Dung T Le, Dirk Jaeger, Emily Chan, Chris Harbison, Chen-Sheng Lin, Marina Tschaika, Alex Azrilevich, Jonathan E Rosenberg
BACKGROUND: Few effective treatments exist for patients with advanced urothelial carcinoma that has progressed after platinum-based chemotherapy. We assessed the activity and safety of nivolumab in patients with locally advanced or metastatic urothelial carcinoma whose disease progressed after previous platinum-based chemotherapy. METHODS: In this phase 1/2, multicentre, open-label study, we enrolled patients (age ≥18 years) with urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra at 16 sites in Finland, Germany, Spain, the UK, and the USA...
October 7, 2016: Lancet Oncology
Kimberly A Homan, David B Kolesky, Mark A Skylar-Scott, Jessica Herrmann, Humphrey Obuobi, Annie Moisan, Jennifer A Lewis
Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen...
October 11, 2016: Scientific Reports
Björn Tampe, Ulrike Steinle, Désirée Tampe, Julienne L Carstens, Peter Korsten, Elisabeth M Zeisberg, Gerhard A Müller, Raghu Kalluri, Michael Zeisberg
Acute kidney injury (AKI) and progressive chronic kidney disease (CKD) are intrinsically tied syndromes. In this regard, the acutely injured kidney often does not achieve its full regenerative capacity and AKI directly transitions into progressive CKD associated with tubulointerstitial fibrosis. Underlying mechanisms of such AKI-to-CKD progression are still incompletely understood and specific therapeutic interventions are still elusive. Because epigenetic modifications play a role in maintaining tissue fibrosis, we used a murine model of ischemia-reperfusion injury to determine whether aberrant promoter methylation of RASAL1 contributes causally to the switch between physiological regeneration and tubulointerstitial fibrogenesis, a hallmark of AKI-to-CKD progression...
September 27, 2016: Kidney International
Gilbert Lefèvre, Francesca Callegari, Sandro Gsteiger, Yuan Xiong
INTRODUCTION: The glomerular filtration rate (GFR), a measure of renal function, decreases by approximately 10 mL/min every 10 years after the age of 40 years, which could lead to the accumulation of drugs and/or renal toxicity. Pharmacokinetic studies of drugs excreted both renally and non-renally are desirable in patients with impaired renal function, defined by parameters including estimated GFR (eGFR) and creatinine clearance (CLCR). OBJECTIVE: We describe here a population pharmacokinetic analysis of the possible effects of renal impairment on steady-state plasma concentrations of rivastigmine and its metabolite NAP226-90 after rivastigmine patch (5 cm(2) [4...
September 28, 2016: Drugs & Aging
John Sarantopoulos, Sanjay Goel, Vincent Chung, Pamela Munster, Shubham Pant, Manish R Patel, Jeffrey Infante, Hussein Tawbi, Carlos Becerra, Justine Bruce, Fairooz Kabbinavar, A Craig Lockhart, Eugene Tan, Shu Yang, Gary Carlson, Jeffrey W Scott, Sunil Sharma
PURPOSE: A capsule formulation of the tyrosine kinase inhibitor dovitinib (TKI258) was recently studied in a phase 3 renal cell carcinoma trial; however, tablets are the planned commercial formulation. Therefore, this randomized 2-way crossover study evaluated the bioequivalence of dovitinib tablet and capsule formulations in pretreated patients with advanced solid tumors, excluding breast cancer. METHODS: In this 2-part study, eligible patients received dovitinib 500 mg once daily on a 5-days-on/2-days-off schedule...
September 28, 2016: Cancer Chemotherapy and Pharmacology
Abdullah K Al-Hwiesh, Ibrahiem S Abdul-Rahman, Abdul-Salam Noor, Mohammed A Nasr-El-Deen, Abdalla Abdelrahman, Tamer S El-Salamony, Fahd A Al-Muhanna, Khalid M Al-Otaibi, Nehad Al-Audah
♦ Objective: Metformin continues to be the safest and most widely used antidiabetic drug. In spite of its well-known benefits; metformin use in end-stage renal disease (ESRD) patients is still restricted. Little has been reported about the effect of peritoneal dialysis (PD) on metformin clearance and the phantom of lactic acidosis deprives ESRD patients from metformin therapeutic advantages. Peritoneal dialysis is probably a safeguard against lactic acidosis, and it is likely that using this drug would be feasible in this group of patients...
September 28, 2016: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
Raktim K Ghosh, Somedeb Ball, Avash Das, Dhrubajyoti Bandyopadhyay, Samhati Mondal, Debjit Saha, Anjan Gupta
Pulmonary arterial hypertension (PAH) is a relatively rare disease which due to its chronic nature has always been difficult to treat effectively. Selexipag is an oral prostacyclin (PGI2) agonist, which was approved by US Food and Drug Administration (US FDA) in December 2015 for the treatment of PAH. After its success in Phase 1 and Phase 2 clinical trials regarding the convenient oral twice daily dosing and low side-effect profile, selexipag raised the hope of controlling the disease progression in PAH patients...
September 27, 2016: Journal of Clinical Pharmacology
Yang Xu, Hongxia Dong, Changhui Ge, Yan Gao, Haifeng Liu, Weiguang Li, Chenggang Zhang
BACKGROUND: Ulcerative colitis (UC) is a nonspecific inflammatory disease for which medications and therapeutic strategies have only been moderately successful. CBLB502, a toll-like receptor 5 (TLR5) agonist derived from Salmonella flagellin, exhibits anticancer and radioprotective activities via modulation of TLRs and the nuclear factor kappa B (NF-κB) signaling pathway and can protect against acute renal ischemic failure. In this study, we intend to examine the effects of CBLB502 on both TLR responses and the interleukin (IL) and NF-κB signaling pathways in UC treatment...
August 2016: Annals of Translational Medicine
Atsuko Tanaka, Ikuko Yano, Keiko Shinsako, Eriko Sato, Masahide Fukudo, Satohiro Masuda, Toshinari Yamasaki, Tomomi Kamba, Osamu Ogawa, Kazuo Matsubara
BACKGROUND: Everolimus has been used for the treatment of unresectable or metastatic renal cell carcinoma (RCC). Here, we measured blood concentrations of everolimus to obtain the population pharmacokinetic parameters and to examine the relationship between blood concentration and clinical outcomes. METHODS: Twenty-two Japanese patients were enrolled. Blood samples were collected before and 2, 4, 8, and 24 h after drug administration on days 1 and 8 of everolimus therapy (5 or 10 mg) for inpatients; occasional samples were collected for outpatients...
September 19, 2016: Therapeutic Drug Monitoring
Rubens Chang, Keisuke Shirai
Patients with end-stage renal disease present with a distinct challenge in oncology. Many anticancer drugs and their metabolites are excreted by the kidney, but data to guide dose and schedule adjustments in renal dialysis are scant. Pembrolizumab is an anti-programmed cell death protein 1 monoclonal antibody proven to be effective in patients with metastatic melanoma. It has demonstrated promising results and was granted US Food and Drug Administration (FDA) approval in September, 2014 for metastatic melanoma...
2016: BMJ Case Reports
Marc Maegele, Oliver Grottke, Herbert Schöchl, Oliver A Sakowitz, Michael Spannagl, Jürgen Koscielny
BACKGROUND: Direct (non-vitamin-K-dependent) oral anticoagulants (DOAC) are given as an alternative to vitamin K antagonists (VKA) to prevent stroke and embolic disease in patients with atrial fibrillation that is not due to pathology of the heart valves. Fatal hemorrhage is rarer when DOACs are given (nonvalvular atrial fibrillation: odds ratio [OR] 0.68; 95% confidence interval [95% CI: 0.48; 0.96], and venous thromboembolism: OR 0.54; [0.22; 1.32]). 48% of emergency trauma patients need an emergency operation or early surgery...
September 5, 2016: Deutsches Ärzteblatt International
Jesús Troya, José Bascuñana
Following the introduction of triple combination therapy in 1996, the paradigm of HIV infection has been modified by its transformation into a chronic disease and thereby significantly reducing its morbidity and mortality. The spectrum of drugs in use since then has changed dramatically with the advent of more potent molecules, new classes of drugs aimed at novel therapeutic targets and their optimization and simplification through fixed-dose combinations that are more convenient for patients, and which, taken together, have led to sustained virologic response rates in treatment-naive patients of more than 90%...
July 2016: AIDS Reviews
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