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Renal excretion of drugs

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https://www.readbyqxmd.com/read/28105769/renal-tubular-resistance-is-the-primary-driver-for-loop-diuretic-resistance-in-acute-heart-failure
#1
Jozine M Ter Maaten, Veena S Rao, Jennifer S Hanberg, F Perry Wilson, Lavanya Bellumkonda, Mahlet Assefa, J Sam Broughton, Julie D'Ambrosi, W H Wilson Tang, Kevin Damman, Adriaan A Voors, David H Ellison, Jeffrey M Testani
BACKGROUND: Loop diuretic resistance is a common barrier to effective decongestion in acute heart failure (AHF), and is associated with poor outcome. Specific mechanisms underlying diuretic resistance are currently unknown in contemporary AHF patients. We therefore aimed to determine the relative importance of defects in diuretic delivery vs. renal tubular response in determining diuretic response (DR) in AHF. METHODS AND RESULTS: Fifty AHF patients treated with intravenous bumetanide underwent a 6-h timed urine collection for sodium and bumetanide clearance...
January 19, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28093773/establishment-of-a-cell-line-for-assessing-drugs-as-canine-p-glycoprotein-substrates-proof-of-principle
#2
K L Mealey, S Dassanayake, N S Burke
P-glycoprotein (P-gp), encoded by the ABCB1 (MDR1) gene, dramatically impacts drug disposition. P-gp is expressed in the intestines, biliary canaliculi, renal tubules, and brain capillaries where it functions to efflux substrate drugs. In this capacity, P-gp restricts oral absorption, enhances biliary and renal excretion, and inhibits central nervous system entry of substrate drugs. Many drugs commonly used in veterinary medicine are known substrates for canine P-gp (vincristine, loperamide, ivermectin, others)...
January 17, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28088910/sodium-glucose-cotransporter-2-inhibitors-sglt2i-their-role-in-cardiometabolic-risk-management
#3
Niki Katsiki, Dimitri P Mikhailidis, Michael J Theodorakis
BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel category of oral antidiabetic drugs that inhibit renal glucose reabsorption and increase renal glucose excretion, thus lowering plasma glucose levels. This unique mechanism of SGLT2i action is insulin independent, thus improving glycemic control without promoting hypoglycemia in the absence of exogenously administered insulin. METHODS: The present narrative review addresses the putative associations between SGLT2i and several cardiovascular (CV) and microvascular risk factors, as well as their effects on cardiac and renal function...
January 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28068585/effects-of-phosphate-binders-on-the-gastrointestinal-absorption-of-arsenate-and-of-an-sglt2-inhibitor-drug-on-the-urinary-excretion-of-arsenite-in-mice
#4
Miklós Poór, Balázs Németi, Zoltán Gregus
Arsenate (As(V)) and arsenite (As(III)) are typical sources of acute and chronic arsenic poisoning. Therefore, reducing inner exposure to these arsenicals is a rational objective. Because As(V) mimics phosphate, phosphate binder drugs may decrease the intestinal As(V) absorption. Indeed, lanthanum and aluminium salts and sevelamer removed As(V) from solution in vitro, especially at acidic pH. In mice gavaged with As(V), lanthanum chloride, lanthanum carbonate and aluminium hydroxide given orally also lowered the urinary excretion and tissue levels of As(V) and its metabolites, indicating that they decreased the gastrointestinal As(V) absorption...
January 3, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28065780/drug-likeness-prediction-of-chemical-constituents-isolated-from-chinese%C3%A2-materia%C3%A2-medica-ciwujia
#5
Shuai-Nan Zhang, Xu-Zhao Li, Xu-Yan Yang
ETHNOPHARMACOLOGICAL RELEVANCE: Ciwujia (CWJ), one of the most commonly used Chinese materia medicas (CMMs), is derived from the roots, rhizomes, and stems of Acanthopanax senticosus harms (AS). CWJ has been used for the treatment of various central nervous system (CNS) and peripheral system diseases. Drug-likeness prediction can help to analyze the absorption, distribution, metabolism, and excretion (ADME) processes of the compounds in CWJ, as well as their potential therapeutic and toxic effects, which is of significance in the confirmation of the active material bases of CWJ...
January 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28061436/multidrug-resistance-transporter-profile-reveals-mdr3-as-a-marker-for-stratification-of-blastemal-wilms-tumour-patients
#6
Lourdes Hontecillas-Prieto, Daniel J Garcia-Dominguez, Diego Pascual Vaca, Rosa Garcia-Mejias, David Marcilla, Gema L Ramirez-Villar, Carmen Saez, Enrique de Álava
Wilms tumour (WT) is the most common renal tumour in children. Most WT patients respond to chemotherapy, but subsets of tumours develop resistance to chemotherapeutic agents, which is a major obstacle in their successful treatment. Multidrug resistance transporters play a crucial role in the development of resistance in cancer due to the efflux of anticancer agents out of cells. The aim of this study was to explore several human multidrug resistance transporters in 46 WT and 40 non-neoplastic control tissues (normal kidney) from patients selected after chemotherapy treatment SIOP 93-01, SIOP 2001...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28057840/delineating-the-role-of-various-factors-in-renal-disposition-of-digoxin-through-application-of-physiologically-based-kidney-model-to-renal-impairment-populations
#7
Daniel Scotcher, Christopher R Jones, Aleksandra Galetin, Amin Rostami-Hodjegan
Development of sub-models of organs within physiologically-based pharmacokinetic (PBPK) principles and beyond simple perfusion limitations may be challenging because of underdeveloped in vitro-in vivo extrapolation approaches or lack of suitable clinical data for model refinement. However, the advantage of such models in predicting clinical observations in divergent patient groups is now commonly acknowledged. Mechanistic understanding of altered renal secretion in renal impairment is one area that may benefit from such models, despite knowledge gaps in renal pathophysiology (Rowland Yeo et al...
January 5, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28049953/cobalt-chloride-induces-expression-and-function-of-breast-cancer-resistance-protein-bcrp-abcg2-in-human-renal-proximal-tubular-epithelial-cell-line-hk-2
#8
Katsuki Nishihashi, Kei Kawashima, Takami Nomura, Yumiko Urakami-Takebayashi, Makoto Miyazaki, Mikihisa Takano, Junya Nagai
The human breast cancer resistance protein (BCRP/ABCG2), a member of the ATP-binding cassette transporter family, is a drug transporter restricting absorption and enhancing excretion of many compounds including anticancer drugs. The cis-regulatory elements in the BCRP promoter include a hypoxia response element, i.e., the DNA binding site for hypoxia-inducible factor-1 (HIF-1). In this study, we investigated the effect of cobalt chloride, a chemical inducer of HIF-1α, on the expression and function of BCRP in human renal proximal tubular cell line HK-2...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28042884/pharmacokinetics-of-the-antimicrobial-drug-sulfanilamide-is-altered-in-a-preclinical-model-of-vascular-calcification
#9
Anabel Brandoni, Adriana Mónica Torres
In vascular smooth muscle, calcium overload is linked to advancing age. The pharmacokinetics of sulfanilamide (SA), a compound with antibacterial properties, was evaluated in a preclinical model of vascular calcification. SA was used since it is useful to study possible modifications in the renal and hepatic management of drugs. Vascular calcification was induced by administration of a single high dose of vitamin D3 to rats (treated group) 10 days before the experiments. A parallel control group was processed...
January 2, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28031343/screening-for-elevated-albuminuria-and-subsequently-hypertension-identifies-subjects-in-which-treatment-may-be-warranted-to-prevent-renal-function-decline
#10
Akin Özyilmaz, Paul E de Jong, Stephan J L Bakker, Sipke T Visser, Chris Thio, Ron T Gansevoort
BACKGROUND: We investigated whether initial population screening for elevated albuminuria with subsequent screening for hypertension in case albuminuria is elevated may be of help to identify subjects at risk for accelerated decline in kidney function. METHODS: We included subjects who participate in the PREVEND observational, general population-based cohort study and had two or more glomerular filtration rate (eGFR) measurements available during follow-up. Elevated albuminuria was defined as an albumin concentration ≥20 mg/L in a first morning urine sample confirmed by an albumin excretion ≥30 mg/day in two 24-h urines...
December 28, 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28013453/pk-pd-target-attainment-with-ceftolozane-tazobactam-using-monte-carlo-simulation-in-patients-with-various-degrees-of-renal-function-including-augmented-renal-clearance-and-end-stage-renal-disease
#11
Alan J Xiao, Luzelena Caro, Myra W Popejoy, Jennifer A Huntington, Ravina Kullar
INTRODUCTION: Ceftolozane/tazobactam is an antibacterial agent with potent in vitro activity against Gram-negative pathogens, including many extended-spectrum β-lactamase-producing Enterobacteriaceae and drug-resistant Pseudomonas aeruginosa. Because ceftolozane/tazobactam is primarily excreted renally, appropriate dose adjustments are needed for patients with renal impairment. Monte Carlo simulations were used to determine the probability of pharmacokinetic/pharmacodynamic target attainment for patients with varying degrees of renal function, including augmented renal clearance (ARC) and end-stage renal disease (ESRD) with hemodialysis...
December 24, 2016: Infectious Diseases and Therapy
https://www.readbyqxmd.com/read/28003189/involvement-of-enac-in-the-development-of-salt-sensitive-hypertension
#12
Tengis S Pavlov, Alexander Staruschenko
Salt-sensitive hypertension is associated with renal and vascular dysfunctions which lead to impaired fluid excretion, increased cardiac output and total peripheral resistance. It is commonly accepted that increased renal sodium handling and plasma volume expansion are necessary factors for the development of salt-induced hypertension. The epithelial sodium channel (ENaC) is a trimeric ion channel expressed in the distal nephron which plays a critical role in the regulation of sodium reabsorption in both normal and pathological conditions...
December 21, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28002117/quantitative-assessment-of-liver-function-using-gadoxetate-enhanced-magnetic-resonance-imaging-monitoring-transporter-mediated-processes-in-healthy-volunteers
#13
Leonidas Georgiou, Jeffrey Penny, Glynis Nicholls, Neil Woodhouse, François-Xavier Blé, Penny L Hubbard Cristinacce, Josephine H Naish
OBJECTIVE: The objective of this study was to use noninvasive dynamic contrast-enhanced magnetic resonance imaging (MRI) techniques to study, in vivo, the distribution and elimination of the hepatobiliary contrast agent gadoxetate in the human body and characterize the transport mechanisms involved in its uptake into hepatocytes and subsequent efflux into the bile using a novel tracer kinetic model in a group of healthy volunteers. MATERIALS AND METHODS: Ten healthy volunteers (age range, 18-29 years), with no history of renal or hepatic impairment, were recruited via advertisement...
February 2017: Investigative Radiology
https://www.readbyqxmd.com/read/27986693/cautious-use-and-optimal-dose-of-morphine-for-relieving-malignant-pain-in-a-complex-patient-with-multiple-comorbidities
#14
Vinod Kumar, Rakesh Garg, Nishkarsh Gupta, Sachidanand Jee Bharati
Oral morphine remains the drug of choice for the management of severe pain due to cancer as per WHO ladder of analgesia. Providing adequate pain relief in palliative care settings for pain due to cancer is challenging. Options become limited in cases of associated systemic comorbidities such as renal dysfunction, hypoproteinaemia, anaemia. Patients with renal dysfunction and other comorbidities may develop drug overdose due to abnormal pharmacokinetics. Renal dysfunction affects the pharmacokinetics of morphine by altering its absorption, metabolism and clearance...
December 16, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27982422/update-review-of-the-acute-porphyrias
#15
REVIEW
Penelope E Stein, Michael N Badminton, David C Rees
Acute porphyrias are rare inherited disorders due to deficiencies of haem synthesis enzymes. To date, all UK cases have been one of the three autosomal dominant forms, although penetrance is low and most gene carriers remain asymptomatic. Clinical presentation is typically with acute neurovisceral attacks characterised by severe abdominal pain, vomiting, tachycardia and hypertension. Severe attacks may be complicated by hyponatraemia, peripheral neuropathy sometimes causing paralysis, seizures and psychiatric features...
December 16, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27981527/examination-of-the-pharmacodynamics-and-pharmacokinetics-of-a-diclofenac-poly-lactic-co-glycolic-acid-nanoparticle-formulation-in-the-rat
#16
S Harirforoosh, K O West, D E Murrell, J W Denham, P C Panus, G A Hanley
OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are assembled into two categories; cyclooxygenase (COX-1) sparing inhibitors of COX-2 and non-selective NSAIDs. Diclofenac (DICLO) is a non-selective NSAID that has been linked to serious side effects including gastric ulcers and renal injury. In this study, we examine the effect of poly(lactic-co-glycolic) acid nanoformulation on DICLO-associated adverse events and pharmacokinetics using a nanoparticle (NP) formulation previously developed in our laboratory...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27951420/-e-2-4-bromophenyl-1-2-4-dihydroxyphenyl-ethanone-oxime-is-a-potential-therapeutic-agent-for-treatment-of-hyperuricemia-through-its-dual-inhibitory-effects-on-xod-and-urat1
#17
Qinghua Hu, Mengze Zhou, Haoran Zhu, Guo Lu, Dongsen Zheng, Huanqiu Li, Kun Hao
Hyperuricemia is a kind of metabolic disease resulted from imbalance between urate production and excretion. Xanthine oxidase (XOD) or renal urate transporter 1 (URAT1) inhibitors have been applied for hyperuricemia treatment in clinic, but available drugs could not simultaneously target XOD and URAT1 and had various adverse effects. (E)-2-(4-bromophenyl)-1-(2, 4-dihydroxyphenyl)ethanone oxime (BDEO), as a deoxybenzoins oxime analog, was obtained from a cluster of deoxybenzoins derivatives synthesized by our research group with potent anti-hyperuricemic activity, which was expected to be dual inhibitor of XOD and URAT1...
December 9, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27943222/clinical-pharmacokinetics-and-pharmacodynamics-of-cediranib
#18
REVIEW
Weifeng Tang, Alex McCormick, Jianguo Li, Eric Masson
Cediranib potently and selectively inhibits all three vascular endothelial growth factor receptors (VEGFR-1, -2 and -3), and clinical studies have shown that it is effective in patients with ovarian cancer at a dose of 20 mg/day. Cediranib is absorbed moderately slowly; a high-fat meal reduced the cediranib area under the plasma concentration-time curve (AUC) by 24% and maximum plasma concentration (C max) by 33%. Cediranib binds to serum albumin and α1-acid glycoprotein; protein binding in human plasma is approximately 95%...
December 9, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27940284/alamethicin-for-using-in-bioavailability-studies-re-evaluation-of-its-effect
#19
Maren Vollmer, Mirko Klingebiel, Sascha Rohn, Ronald Maul
A major pathway for the elimination of drugs is the biliary and renal excretion following the formation of more hydrophilic secondary metabolites such as glucuronides. For in vitro investigations of the phase II metabolism, hepatic microsomes are commonly used in the combination with the pore-forming peptide alamethicin, also to give estimates for the in vivo situation. Thus, alamethicin may represent a neglected parameter in the characterization of microsomal in vitro assays. In the present study, the influence of varying alamethicin concentrations on glucuronide formation of selected phenolic compounds was investigated systematically...
March 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27940129/a-systematic-meta-analysis-on-the-efficacy-of-pre-clinically-tested-nephroprotectants-at-preventing-aminoglycoside-nephrotoxicity
#20
REVIEW
Laura Vicente-Vicente, Alfredo G Casanova, María Teresa Hernández-Sánchez, Moisés Pescador, Francisco J López-Hernández, Ana Isabel Morales
Nephrotoxicity limits the use of aminoglycoside antibiotics. Kidney damage is produced mainly in the renal tubule due to an inflammatory and oxidative process. At preclinical level, many drugs and natural products have been tested as prospective protectors of aminoglycoside nephrotoxicity. The main objective of this work was to make a systematic literature review of preclinical studies about aminoglycoside nephrotoxicity protection and a statistical analysis based on the meta-analysis methodology. Studies published up to January 2016 were identified...
December 8, 2016: Toxicology
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