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Renal excretion of drugs

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https://www.readbyqxmd.com/read/28322496/comparison-of-hydrodynamically-closed-two-dimensional-capillary-electrophoresis-coupled-with-ultraviolet-detection-and-hydrodynamically-open-capillary-electrophoresis-hyphenated-with-mass-spectrometry-in-the-bioanalysis-of-varenicline
#1
Juraj Piešťanský, Katarína Maráková, Jaroslav Galba, Andrej Kováč, Peter Mikuš
Two capillary electrophoresis methods for monitoring renally excreted varenicline, a highly effective drug prescribed for smoking cessation, in human urine were developed and compared. A method combining capillary electrophoresis with mass spectrometry was proposed for the fast analysis of varenicline (analysis time up to 7 min). Here, mass spectrometry was a prerequisite for achieving high sensitivity and selectivity of the analysis suitable for the quantification of a 15 ng.mL(-1) level of varenicline in un-pretreated urine matrices...
March 21, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28303514/euglycemic-ketosis-in-patients-with-type-2-diabetes-on-sglt2-inhibitor-therapy-an-emerging-problem-and-solutions-offered-by-diabetes-technology
#2
A Pfützner, D Klonoff, L Heinemann, N Ejskjaer, J Pickup
Diabetic ketoacidosis is an infrequent but life-threatening acute complication of diabetes, affecting predominantly patients with type 1 diabetes, children, and pregnant women, where ketosis is usually associated with marked hyperglycemia. Recently, an increasing number of cases have been reported of euglycemic diabetic ketoacidosis in patients with type 2 diabetes receiving sodium-glucose cotransporter 2 inhibitor treatment in routine practice. There is a minor, but not negligible diabetic ketoacidosis risk associated with this drug class, which was not seen in randomized clinical trials...
March 17, 2017: Endocrine
https://www.readbyqxmd.com/read/28298174/the-involvement-of-multidrug-and-toxin-extrusion-protein-1-in-the-distribution-and-excretion-of-berberine
#3
Ling Xiao, Yaru Xue, Cuifeng Zhang, Le Wang, Yunfei Lin, Guoyu Pan
1. Berberine (BBR), an isoquinoline alkaloid, has demonstrated multiple clinical pharmacological actions. As a substrate of multiple transporters in the liver, BBR is rarely excreted into the bile but can be found in the urine. The purpose of the present study was to investigate the role of multidrug and toxin extrusion protein 1 (MATE1) in the transport of BBR in the liver and kidney. 2. Using human MATE1 (hMATE1)-transfected HEK293 cells, BBR was shown to be a substrate of hMATE1 (Km = 4.28 ± 2.18 μM)...
March 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28292990/-nephropathy-in-patients-undergoing-cancer-drug-therapy-platinum-derivatives-cisplatin-and-carboplatin
#4
Ayumu Matsuoka, Yuichi Ando
Cisplatin, a first-generation platinum derivative, is one of the most widely used anticancer agents and can treat a broad spectrum of malignancies. Cisplatin-induced nephrotoxicity is a major dose-limiting side effect resulting from damage to the proximal tubules of the kidney. This nephrotoxicity can be prevented by lowering the concentration of cisplatin and shortening the period of cisplatin exposure to the proximal tubules. In clinical practice, high-volume hydration(>3 L intravenous isotonic saline), forced diuresis(mannitol and/or furosemide), and magnesium supplementation have been generally used to lower the risk of cisplatin-induced nephrotoxicity...
March 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28284381/mechanisms-of-drug-induced-interstitial-nephritis
#5
REVIEW
Rajeev Raghavan, Saed Shawar
Drug-induced acute interstitial nephritis (DI-AIN) is a drug hypersensitivity reaction (DHR) that manifests 7 to 10 days after exposure to the culprit drug. DHRs account for fewer than 15% of reported adverse drug reactions. The kidneys are susceptible to DHR because: (1) the high renal blood flow whereby antigens are filtered, secreted, or concentrated, and (2) it is a major site of excretion for drugs and drug metabolites. More than 250 different drugs from various classes have been incriminated as causative agents of DI-AIN, the third most common cause of acute kidney injury in the hospital...
March 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/28277164/pharmacokinetics-of-the-selective-prostacyclin-receptor-agonist-selexipag-in-rats-dogs-and-monkeys
#6
Tomohiko Ichikawa, Tetsuhiro Yamada, Alexander Treiber, Carmela Gnerre, Kiyoko Nonaka
1. This study examined the pharmacokinetics, distribution, metabolism and excretion of the selective prostacyclin receptor agonist selexipag (NS-304; ACT-293987) and its active metabolite MRE-269 (ACT-33679). The compounds were investigated following oral and/or intravenous administration to intact rats, dogs and monkeys, and bile-duct-cannulated rats and dogs. 2. After oral administration of [(14)C]selexipag, selexipag was well absorbed in rats and dogs with total recoveries of over 90% of the dose, mainly in the faeces...
March 2, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28271063/pharmacokinetics-of-standard-and-reduced-dose-recombinant-human-soluble-thrombomodulin-in-patients-with-septic-disseminated-intravascular-coagulation-during-continuous-hemodiafiltration
#7
Eizo Watanabe, Shingo Yamazaki, Daisuke Setoguchi, Tomohito Sadahiro, Yoshihisa Tateishi, Tatsuya Suzuki, Itsuko Ishii, Shigeto Oda
INTRODUCTION: Recombinant human soluble thrombomodulin (rTM) is reportedly excreted by the kidneys; therefore, the recommended dose for patients with renal impairment is one-third of the standard dose. The aim of this study was to evaluate whether this reduced dose of rTM achieves effective drug concentrations that are comparable to those of the standard dose in treating sepsis-induced disseminated intravascular coagulation (DIC) during continuous hemodiafiltration (CHDF). METHODS: Eight patients in an intensive care unit were randomized to receive either reduced-dose (0...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28270811/animal-models-of-leptospirosis-of-mice-and-hamsters
#8
REVIEW
Maria Gomes-Solecki, Ignacio Santecchia, Catherine Werts
Pathogenic Leptospira sp. are spirochetal bacteria responsible for leptospirosis, an emerging worldwide zoonosis. These spirochetes are very successful pathogens that infect a wide range of hosts such as fish, reptiles, birds, marsupials, and mammals. Transmission occurs when chronically infected animals excrete live bacteria in their urine, contaminating the environment. Leptospira sp. enter their hosts through damaged skin and mucosa. Chronically infected rats and mice are asymptomatic and are considered as important reservoirs of the disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28270565/midostaurin-a-novel-protein-kinase-inhibitor-for-the-treatment-of-acute-myelogenous-leukemia-insights-from-human-absorption-metabolism-and-excretion-studies-of-a-bddcs-ii-drug
#9
Handan He, Phi Tran, Helen Gu, Vivienne Tedesco, Jin Zhang, Wen Lin, Ewa Gatlik, Kai Klein, Tycho Heimbach
The absorption, metabolism and excretion of midostaurin, a potent class III tyrosine protein kinase inhibitor for acute myelogenous leukemia, were evaluated in healthy subjects. A microemulsion formulation was chosen to optimize absorption. After a 50 mg [14C]midostaurin dose, oral absorption was high (> 90%) and relatively rapid. In plasma, the major circulating components were midostaurin (22%), CGP52421 (32.7%), and CGP62221 (27.7%). Long plasma half-lives were observed for midostaurin (20.3 h), CGP52421 (495 h), and CGP62221 (33...
March 7, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28240771/inappropriate-medication-in-non-hospitalized-patients-with-renal-insufficiency-a-systematic-review
#10
Michael Dörks, Katharina Allers, Guido Schmiemann, Stefan Herget-Rosenthal, Falk Hoffmann
OBJECTIVES: Renal insufficiency is common among older patients and, accordingly, renally excreted drugs may require an adjustment in dosage for them. Rates of non-adherence to renal dosing guidelines range from 19% to 70% across all settings, with the highest rate occurring in outpatient care. However, there is a paucity of research in this field. The main objective of this systematic review is to assess how often drugs are inappropriately prescribed in non-hospitalized patients with renal insufficiency...
February 27, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28236252/clinical-pharmacokinetics-of-paritaprevir
#11
REVIEW
Rajeev M Menon, Akshanth R Polepally, Amit Khatri, Walid M Awni, Sandeep Dutta
Paritaprevir is a potent hepatitis C virus (HCV) nonstructural (NS) protein 3/4A protease inhibitor that is used in combination with other direct-acting antivirals (DAAs) for the treatment of chronic HCV infection. Paritaprevir is primarily metabolized by cytochrome P450 (CYP) 3A4 and is administered with a low dose of ritonavir to achieve drug concentrations suitable for once-daily dosing. Coadministration of paritaprevir with ritonavir increases the half-life of single-dose paritaprevir from approximately 3 h to 5-8 h, doubles the time to maximum plasma concentration (T max) from 2...
February 25, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28236116/clinical-pharmacokinetic-and-pharmacodynamic-profile-of-lenvatinib-an-orally-active-small-molecule-multitargeted-tyrosine-kinase-inhibitor
#12
Ziad Hussein, Hitoshi Mizuo, Seiichi Hayato, Masayuki Namiki, Robert Shumaker
Lenvatinib is a multikinase inhibitor that targets vascular endothelial growth factor (VEGF) receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor-alpha, and RET and KIT proto-oncogenes. Lenvatinib is approved for the treatment of radioiodine-refractory differentiated thyroid cancer in the United States (US), European Union (EU), Canada, Japan, and Switzerland. It is also approved in combination with everolimus for the treatment of advanced renal cell carcinoma following ≥1 VEGF-targeted treatment in the US and EU...
February 24, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28229375/clinical-pharmacokinetics-of-ombitasvir
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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: Multidrug resistance protein-2 encoded by the ABCC2 gene (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...
April 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
#19
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...
April 1, 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
#20
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
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