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Renal excretion of drugs

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https://www.readbyqxmd.com/read/28229375/clinical-pharmacokinetics-of-ombitasvir
#1
REVIEW
Prajakta S Badri, Diana L Shuster, Sandeep Dutta, Rajeev M Menon
Ombitasvir is a potent, nonstructural protein 5A inhibitor of the hepatitis C virus (HCV) that is used in combination with other direct-acting antivirals for the treatment of chronic HCV infection. Ombitasvir is predominantly metabolized by amide hydrolysis followed by oxidative metabolism and is a substrate of P-glycoprotein. Ombitasvir displays linear pharmacokinetics with minimal accumulation and is eliminated via metabolism and biliary excretion. A negligible amount of unchanged drug is excreted in urine...
February 22, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28220713/the-influence-of-targeted-temperature-management-on-the-pharmacokinetics-of-drugs-administered-during-and-after-cardiac-arrest-a-systematic-review
#2
Tessa Crombez, Said Hachimi-Idrissi
OBJECTIVE: Pharmacokinetic parameters of drugs are widely investigated under normothermic conditions and normal hemodynamic parameters. The European Resuscitation Council recommends the use of targeted temperature management (TTM) with a target temperature of 34 °C in cardiac arrest (CA) patients. The aim of this literature review is to investigate the influence of CA combined with TTM on the pharmacokinetics of drugs. Results of preclinical and clinical studies are compared with each other...
February 21, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28210512/porphyria-cutanea-tarda-in-a-patient-with-end-stage-renal-disease-a-case-of-successful-treatment-with-deferoxamine-and-ferric-carboxymaltose
#3
Natacha Rodrigues, Fernando Caeiro, Alice Santana, Teresa Mendes, Leonor Lopes
Porphyria cutanea tarda (PCT) is a rare disease, with a strong association with hepatitis C virus. PCT is particularly problematic in end-stage renal disease patients as they have no renal excretion of porphyrins and these are poorly dialyzed. Also, conventional treatment of PCT is compromised in these patients as hydroxychloroquine is contraindicated, phlebotomies with the stipulated frequency are poorly tolerated in already anaemia-prone patients, and iron-chelating agents are less efficient in removing iron and contribute to worsening anaemia...
2017: Case Reports in Nephrology
https://www.readbyqxmd.com/read/28210286/bilastine-in-allergic-rhinoconjunctivitis-and-urticaria-a-practical-approach-to-treatment-decisions-based-on-queries-received-by-the-medical-information-department
#4
REVIEW
Amalia Leceta, Ander Sologuren, Román Valiente, Cristina Campo, Luis Labeaga
BACKGROUND: Bilastine is a safe and effective commonly prescribed non-sedating H1-antihistamine approved for symptomatic treatment in patients with allergic disorders such as rhinoconjunctivitis and urticaria. It was evaluated in many patients throughout the clinical development required for its approval, but clinical trials generally exclude many patients who will benefit in everyday clinical practice (especially those with coexisting diseases and/or being treated with concomitant drugs)...
2017: Drugs in Context
https://www.readbyqxmd.com/read/28203304/muscle-spasms-an-unexpected-adverse-drug-reaction-of-pemetrexed
#5
REVIEW
Hendrika J A de Rouw, Naomi T Jessurun, Lucie J P Masen-Poos, Hieronymus J Derijks
In this report we describe a 53-year-old woman with advanced non-small cell lung cancer, treated with pemetrexed and cisplatin combination therapy, followed by pemetrexed monotherapy. The patient developed severe muscle spasms at least twice, shortly after administration of pemetrexed monotherapy. A possible explanation for this observation is that in combination with cisplatin therapy, the patient was hyperhydrated before administration to promote renal excretion and reduce toxicity. Pemetrexed is also renally excreted, which supports the finding that toxicity did not occur when the patient was hyperhydrated...
February 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28196047/a-time-dependent-model-describes-methotrexate-elimination-and-supports-dynamic-modification-of-mrp2-abcc2-activity
#6
Jean-Baptiste Woillard, Jean Debord, Isabelle Benz-de-Bretagne, Franck Saint-Marcoux, Pascal Turlure, Stéphane Girault, Julie Abraham, Sylvain Choquet, Pierre Marquet, Chantal Barin-Le Guellec
BACKGROUND: MRP2/ABCC2, an efflux transporter expressed at the proximal renal tubule, is rate limiting for urine excretion of coproporphyrin (UCP) isomers I and III, translating in high UCP (I/(I+III)) ratio in MRP2-deficient patients presenting with the Dubin-Johnson Syndrome. MRP2 is also a major contributor to methotrexate (MTX) clearance. As MTX is both a substrate and an inhibitor of MRP2, time course of the concentrations of MTX in blood could induce functional modification of MRP2 over time, which in turn can modify its own elimination rate...
February 11, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28185988/effects-of-nonsteroidal-anti-inflammatory-drugs-on-the-renal-excretion-of-indoxyl-sulfate-a-nephro-cardiovascular-toxin-in-rats
#7
Chung-Ping Yu, Douglas H Sweet, Yu-Hsuan Peng, Yow-Wen Hsieh, Pei-Dawn Lee Chao, Yu-Chi Hou, Shiuan-Pey Lin
Chronic kidney disease (CKD) is a health problem worldwide. Indoxyl sulfate (IS) is a nephro-cardiovascular toxin accumulated in CKD patients and cannot be removed through hemodialysis. The renal excretion of IS was mediated by organic anion transporters (OATs) OAT 1 and OAT 3. Because a number of nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to inhibit OATs, we hypothesize that NSAIDs might inhibit the renal excretion of IS. Rats were intravenously injected IS with and without diclofenac, ketoprofen or salicylic acid, individually...
February 7, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28181269/-99m-tc-tazobactam-a-novel-infection-imaging-agent-radiosynthesis-quality-control-biodistribution-and-infection-imaging-studies
#8
Rashid Rasheed, Syed Ali Raza Naqvi, Syed Jawad Hussain Gillani, Ameer Fawad Zahoor, Asif Jielani, Nidda Saeed
The radiolabeled drug (99m) Tc-tazobactam ((99m) Tc-TZB) was developed and assessed as an infection imaging agent in P. aeruginosa and S. enterica infection induced animal models by comparing with inflammation induced animal models. Radiosynthesis of (99m) Tc-TZB was assessed while changing ligand concentration, reducing agent concentration, pH and reaction time while keeping radioactivity constant (~370 MBq). Percent labeling of the resulting complex was measured using paper chromatography and instant thin layer chromatography (ITLC-SG)...
February 8, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28161805/mate-1-modulation-by-kinin-b1-receptor-enhances-cisplatin-efflux-from-renal-cells
#9
Gabriel R Estrela, Frederick Wasinski, Raphael J F Felizardo, Laura L Souza, Niels O S Câmara, Michael Bader, Ronaldo C Araujo
Cisplatin is a drug widely used in chemotherapy that frequently causes severe renal dysfunction. Organic transporters have an important role to control the absorption and excretion of cisplatin in renal cells. Deletion and blockage of kinin B1 receptor has already been show to protect against cisplatin-induced acute kidney injury. To test whether it exerts its protective function by modulating the organic transporters in kidney, we studied kinin B1 receptor knockout mice and treatment with a receptor antagonist at basal state and in presence of cisplatin...
February 4, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28147361/enantioselective-effect-of-flurbiprofen-on-lithium-disposition-in-rats
#10
Yuichi Uwai, Masashi Matsumoto, Tatsuya Kawasaki, Tomohiro Nabekura
AIMS: Lithium is administered for treating bipolar disorders and is mainly excreted into urine. Nonsteroidal anti-inflammatory drugs inhibit this process. In this study, we examined the enantioselective effect of flurbiprofen on the disposition of lithium in rats. METHODS: Pharmacokinetic experiments with lithium were performed. RESULTS: Until 60 min after the intravenous administration of lithium chloride at 30 mg/kg as a bolus, 17.8% of lithium injected was recovered into the urine...
February 2, 2017: Pharmacology
https://www.readbyqxmd.com/read/28143610/severe-toxicity-induced-by-accumulation-of-active-sunitinib-metabolite-in-a-japanese-patient-with-renal-cell-carcinoma-a-case-report
#11
Shinya Takasaki, Masafumi Kikuchi, Yoshihide Kawasaki, Akihiro Ito, Yoichi Arai, Hiroaki Yamaguchi, Nariyasu Mano
BACKGROUND: Sunitinib is a multi-targeted tyrosine kinase inhibitor that is approved for treatment of renal cell carcinoma as an oral anticancer drug. Therapeutic drug monitoring of total sunitinib (sunitinib and N-desethyl sunitinib) is used in our hospital to improve therapeutic efficacy, while preventing adverse effects. Here, we report the first case of a patient with metastatic renal cell carcinoma undergoing hemodialysis and presenting severe adverse events induced by the accumulation of N-desethyl sunitinib...
February 1, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28129817/-dalbavancin-pharmacokinetic-and-pharmacodynamic-parameters
#12
José Ramón Azanza, Belén Sádaba, Joana Reis
Dalbavancin is a new lipoglycopeptide antibiotic whose structure influences its pharmacokinetic profile. It is not absorbed after oral administration and is therefore administered intravenously. It is distributed through intracellular fluid, reaching adequate concentrations in the skin, bone, blister fluid and synovial fluid. Plasma protein binding is very high. Concentrations in brain tissue and cerebrospinal fluid (CSF) are inadequate. Excretion is through non-microsomal metabolism with inactive metabolites and through the kidneys by glomerular filtration...
January 2017: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/28111348/xenobiotic-transporters-and-kidney-injury
#13
REVIEW
Blessy George, Dahea You, Melanie S Joy, Lauren M Aleksunes
Renal proximal tubules are targets for toxicity due in part to the expression of transporters that mediate the secretion and reabsorption of xenobiotics. Alterations in transporter expression and/or function can enhance the accumulation of toxicants and sensitize the kidneys to injury. This can be observed when xenobiotic uptake by carrier proteins is increased or efflux of toxicants and their metabolites is reduced. Nephrotoxic chemicals include environmental contaminants (halogenated hydrocarbon solvents, the herbicide paraquat, the fungal toxin ochratoxin, and heavy metals) as well as pharmaceuticals (certain beta-lactam antibiotics, antiviral drugs, and chemotherapeutic drugs)...
January 20, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28105769/renal-tubular-resistance-is-the-primary-driver-for-loop-diuretic-resistance-in-acute-heart-failure
#14
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
#15
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
#16
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
#17
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 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
#18
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
#19
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
#20
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
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