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Renal excretion of drugs

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https://www.readbyqxmd.com/read/29353349/daclatasvir-a-review-of-preclinical-and-clinical-pharmacokinetics
#1
REVIEW
Yash Gandhi, Timothy Eley, Aberra Fura, Wenying Li, Richard J Bertz, Tushar Garimella
Daclatasvir is a first-in-class, highly selective, hepatitis C virus, non-structural protein 5a polymerase replication complex inhibitor with picomolar potency and broad genotypic coverage in vitro. Daclatasvir undergoes rapid absorption, with a time to reach maximum plasma concentration of 1-2 h and an elimination half-life of ~ 10 to 14 h observed in single-ascending dose studies. Steady state was achieved by day 4 in multiple-ascending dose studies. Daclatasvir can be administered without regard to food or pH modifiers...
January 20, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29338456/an-update-on-the-safety-of-nutraceuticals-and-effects-on-lipid-parameters
#2
Arrigo F G Cicero, Alessandro Colletti
Cardiovascular diseases (CVDs) are the leading cause of mortality and disability in developed countries, whereas a large portion of patients in primary prevention have uncontrolled level of CVD risk factors. Dietary supplementation with bioactive natural compounds with demonstrated lipid-lowering effects is currently supported by the international guidelines for CVD prevention and some international expert panels. Areas covered: This review provides insights on issues concerning the tolerability and safety of the most commonly used nutraceuticals with demonstrated lipid-lowering effect in humans...
January 16, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29322928/constraint-based-perturbation-analysis-with-cluster-newton-method-a-case-study-of-personalized-parameter-estimations-with-irinotecan-whole-body-physiologically-based-pharmacokinetic-model
#3
Shun Asami, Daisuke Kiga, Akihiko Konagaya
BACKGROUND: Drug development considering individual varieties among patients becomes crucial to improve clinical development success rates and save healthcare costs. As a useful tool to predict individual phenomena and correlations among drug characteristics and individual varieties, recently, whole-body physiologically based pharmacokinetic (WB- PBPK) models are getting more attention. WB-PBPK models generally have a lot of drug-related parameters that need to be estimated, and the estimations are difficult because the observed data are limited...
December 21, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/29320949/absorption-distribution-metabolism-and-excretion-of-an-isocitrate-dehydrogenase-2-inhibitor-enasidenib-in-rats-and-humans
#4
Zeen Tong, Christian Atsriku, Usha Yerramilli, Xiaomin Wang, Yan Li, Josephine Reyes, Bin Fan, Hua Yang, Matthew Hoffmann, Sekhar Surapaneni
1. The absorption, distribution, metabolism and excretion (ADME) of enasidenib were studied following a single oral dose of [14C]enasidenib to rats (10 mg/kg; 100 μCi/kg) and healthy volunteers (100 mg; 318 nCi). 2. Enasidenib was readily absorbed, extensively metabolized and primarily eliminated via the hepatobiliary pathway. Enasidenib-derived radioactivity was widely distributed in rats. Excretion of radioactivity was approximately 95% to 99% of the dose from rats in 168 hours post-dose and 82.4% from human volunteers in 504 hours post-dose...
January 10, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29316186/organ-damage-changes-in-patients-with-resistant-hypertension-randomized-to-renal-denervation-or-spironolactone-the-denervhta-denervaci%C3%A3-n-en-hipertensi%C3%A3-n-arterial-study
#5
Anna Oliveras, Pedro Armario, Laia Sans, Albert Clarà, Susana Vázquez, Luis Molina, Júlia Pareja, Alejandro de la Sierra, Julio Pascual
Renal denervation and spironolactone have both been proposed for the treatment of resistant hypertension, but their effects on preclinical target organ damage have not been compared. Twenty-four patients with 24-hour systolic blood pressure ≥140 mm Hg despite receiving three or more full-dose antihypertensive drugs, one a diuretic, were randomized to receive spironolactone or renal denervation. Changes in 24-hour blood pressure, urine albumin excretion, arterial stiffness, carotid intima-media thickness, and left ventricular mass index were evaluated at 6 months...
January 5, 2018: Journal of Clinical Hypertension
https://www.readbyqxmd.com/read/29311252/pazopanib-induced-hypertension-in-patients-with-renal-cell-carcinoma-is-associated-with-low-urine-excretion-of-no-metabolites
#6
Anne Robdrup Tinning, Camilla Bengtsen, Niels Viggo Jensen, Lars Bastholt, Boye Lagerbon Jensen, Kirsten Madsen
Drugs targeting VEGF (vascular endothelial growth factor) are often associated with rapid development of hypertension by a yet not fully understood mechanism. VEGF is expressed in renal epithelial cells and stimulates NO production. In the renal medulla, inhibition of NO formation by local L-NAME or by impaired endothelin-1 leads to hypertension. The present study was designed to test the hypothesis that VEGF receptor inhibitor treatment leads to hypertension through decreased renal medullary formation of NO and endothelin-1...
January 8, 2018: Hypertension
https://www.readbyqxmd.com/read/29297694/renal-clearable-hollow-bismuth-subcarbonate-nanotubes-for-tumor-targeted-ct-imaging-and-chemoradiotherapy
#7
Xi Hu, Jihong Sun, Fangyuan Li, Ruiqing Li, Jiahe Wu, Jie He, Nan Wang, Jianan Liu, Shuaifei Wang, Fei Zhou, Xiaolian Sun, Dokyoon Kim, Taeghwan Hyeon, Daishun Ling
Although metallic nanomaterials with high X-ray attenuation coefficients have been wide-ly used as X-ray computed tomography (CT) contrast agents, their intrinsically poor bio-degradability requires them to be cleared from the body to avoid any potential toxicity. On the other hand, extremely small-sized nanomaterials with outstanding renal clearance properties are not much effective for tumor targeting because of their too rapid clearance in vivo. To overcome this dilemma, here we report on the hollow bismuth subcarbonate nanotubes (BNTs) assembled from renal-clearable ultrasmall bismuth subcarbonate nanoclusters for tumor-targeted imaging and chemoradiotherapy...
January 3, 2018: Nano Letters
https://www.readbyqxmd.com/read/29296186/genetic-variants-associated-with-fabry-disease-progression-despite-enzyme-replacement-therapy
#8
Francesca Scionti, Maria Teresa Di Martino, Simona Sestito, Angela Nicoletti, Francesca Falvo, Katia Roppa, Mariamena Arbitrio, Pietro Hiram Guzzi, Giuseppe Agapito, Antonio Pisani, Eleonora Riccio, Daniela Concolino, Licia Pensabene
Enzyme replacement therapy (ERT) has been widely used for the treatment of Fabry disease, a rare X-linked recessive disorder due to absent or reduced activity of lysosomal enzyme α-galactosidase A. It is still unclear why some patients under ERT show disease progression typically with renal, cardiovascular and cerebrovascular dysfunctions. Here, we investigated the involvement of drug absorption, distribution, metabolism, and excretion gene variants in response variability to ERT, genotyping 37 patients with the Affymetrix Drug Metabolizing Enzyme and Transporters (DMET) Plus microarray...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29277663/oat1-and-oat3-also-mediate-the-drug-drug-interaction-between-piperacillin-and-tazobactam
#9
Shijie Wen, Changyuan Wang, Yingjie Duan, Xiaokui Huo, Qiang Meng, Zhihao Liu, Shilei Yang, Yanna Zhu, Huijun Sun, Xiaodong Ma, Siyun Yang, Kexin Liu
This study aimed to demonstrate that organic anion transporters (OATs) mediate the drug-drug interaction (DDI) between piperacillin and tazobactam. After co-administration with piperacillin in rats, the AUC of tazobactam in plasma was significantly increased, and t1/2β was prolonged with significant reduction in plasma clearance, renal clearance and cumulative urinary excretion. In rat and human kidney slices, probenecid, p-aminohippurate and benzylpenicillin inhibited the uptake of piperacillin and tazobactam...
December 22, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29258368/lisdexamfetamine-chemistry-pharmacodynamics-pharmacokinetics-and-clinical-efficacy-safety-and-tolerability-in-the-treatment-of-binge-eating-disorder
#10
Kristen Ward, Leslie Citrome
The indications for lisdexamfetamine (LDX), a central nervous system stimulant, were recently expanded to include treatment of moderate to severe binge eating disorder (BED). Areas covered: This review aims to describe the chemistry and pharmacology of LDX, as well as the clinical trials investigating the efficacy and safety of this medication for the management of BED. Expert opinion: LDX is the first medication with United States Food and Drug Administration approval for the treatment of BED. It is an inactive prodrug of d-amphetamine that extends the half-life of d-amphetamine to allow for once daily dosing...
January 4, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29230684/imipenem-relebactam-and-meropenem-vaborbactam-two-novel-carbapenem-%C3%AE-lactamase-inhibitor-combinations
#11
REVIEW
George G Zhanel, Courtney K Lawrence, Heather Adam, Frank Schweizer, Sheryl Zelenitsky, Michael Zhanel, Philippe R S Lagacé-Wiens, Andrew Walkty, Andrew Denisuik, Alyssa Golden, Alfred S Gin, Daryl J Hoban, Joseph P Lynch, James A Karlowsky
Relebactam (formerly known as MK-7655) is a non-β-lactam, bicyclic diazabicyclooctane, β-lactamase inhibitor that is structurally related to avibactam, differing by the addition of a piperidine ring to the 2-position carbonyl group. Vaborbactam (formerly known as RPX7009) is a non-β-lactam, cyclic, boronic acid-based, β-lactamase inhibitor. The structure of vaborbactam is unlike any other currently marketed β-lactamase inhibitor. Both inhibitors display activity against Ambler class A [including extended-spectrum β-lactamases (ESBLs), Klebsiella pneumoniae carbapenemases (KPCs)] and class C β-lactamases (AmpC)...
December 12, 2017: Drugs
https://www.readbyqxmd.com/read/29227582/role-of-the-sodium-hydrogen-exchanger-in-mediating-the-renal-effects-of-drugs-commonly-used-in-the-treatment-of-type-2-diabetes
#12
REVIEW
Milton Packer
Diabetes is characterized by an increased activity of the sodium-hydrogen exchanger (NHE) in the glomerulus and renal tubules, which contributes importantly to the development of nephropathy. Despite the established role played by the exchanger in experimental studies, it has not been specifically targeted by those seeking to develop novel pharmacological treatments for diabetes. This review demonstrates that many existing drugs that are commonly prescribed to patients with diabetes act on the NHE1 and NHE3 isoforms in the kidney...
December 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29197971/comparison-of-long-term-follow-up-outcomes-between-multiple-drugs-combination-therapy-and-tonsillectomy-pulse-therapy-for-pediatric-iga-nephropathy
#13
Yukihiko Kawasaki, Ryo Maeda, Syuto Kanno, Yuichi Suzuki, Shinichiro Ohara, Kazuhide Suyama, Mitsuaki Hosoya
BACKGROUND: To clarify the long-term efficacy of multiple-drugs combination therapy (PWDM) and tonsillectomy pulse therapy (TPT) for pediatric IgA nephropathy (IgAN), we retrospectively evaluated the clinical and laboratory findings as well as the prognosis for IgAN patients treated with each treatment at long-term follow-up. METHODS: We collected data on 61 children who had been diagnosed with severe IgAN. The children were retrospectively divided into two groups...
December 2, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29191019/affinity-of-ketamine-to-clinically-relevant-transporters
#14
Markus Keiser, Mahmoud Hasan, Stefan Oswald
Ketamine is a widely used intravenous anaesthetic drug that has also a pronounced analgesic effect. Moreover, one of its metabolites was very recently shown to possess antidepressant activity. Consequently, oral administration of ketamine may become of interest in the future. There is evidence from in vitro data, drug-drug interactions and from the physicochemical properties of the drug that ketamine may be a substrate of drug transporters. Thus, it was the aim of this study to investigate the affinity of ketamine to clinically relevant transporter proteins that are expected to affect its intestinal absorption, distribution and excretion...
November 30, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29187381/crrl269-a-novel-designer-and-renal-enhancing-pgc-a-peptide-activator
#15
Yang Chen, Gail J Harty, Brenda K Huntley, Seethalakshmi R Iyer, Denise M Heublein, Gerald E Harders, Laura M G Meems, Shuchong Pan, S Jeson Sangaralingham, Tomoko Ichiki, John C Burnett
AIMS: The natriuretic peptides (NPs) b-type NP (BNP) and urodilatin (URO) exert renal protective properties via the particulate guanylyl cyclase A receptor (pGC-A). As a potential renal enhancing strategy, we engineered a novel designer peptide that we call CRRL269. CRRL269 was investigated in human cell lines and in normal canines to define potential cardiorenal enhancing actions. The mechanism of its cardiorenal selective properties was also investigated. METHODS AND RESULTS: In vitro NP receptor activity was quantified with 3', 5' cyclic guanosine monophosphate (cGMP) generation...
November 29, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29187007/glecaprevir-pibrentasvir-abt493-abt-530-for-the-treatment-of-hepatitis-c
#16
Hope Hubbard, Eric Lawitz
Glecaprevir (formerly ABT-493, pangenotypic NS3/4A protease inhibitor) and pibrentasvir (formerly ABT-530, pangenotypic NS5A inhibitor) are second generation direct acting antivirals (DAA) for the treatment of chronic Hepatitis C (HCV). It is a fixed dose ribavirin (RBV)-free regimen with activity against genotypes (GT) 1-6. In vitro the two antivirals have synergistic activity with a high barrier to resistance and potent activity against common polymorphisms. It is once daily oral dosing with minimal absorption, primary biliary excretion, and negligible renal excretion, making it safe for patients with renal impairment...
January 2018: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29178575/serum-iga-c3-and-glomerular-c3-staining-predict-severity-of-iga-nephropathy
#17
Yukihiko Kawasaki, Ryo Maeda, Shinichiro Ohara, Kazuhide Suyama, Mitsuaki Hosoya
BACKGROUND: We evaluated whether the serum IgA/C3 ratio and glomerular C3 staining predict prognosis in IgA nephropathy. METHODS: We collected data for 44 IgA nephropathy children treated with multi-drug combination therapy. The children were retrospectively divided into four groups based on the serum IgA/C3 ratio and glomerular C3 staining. Group A consisted of 9 children with a higher than median IgA/C3 ratio and glomerular C3 staining ≧2.0, Group B consisted of 7 children with a higher than median IgA/C3 ratio and glomerular C3 staining <2...
November 27, 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/29177954/pharmacogenetic-study-of-the-impact-of-abcb1-single-nucleotide-polymorphisms-on-lenalidomide-treatment-outcomes-in-patients-with-multiple-myeloma-results-from-a-phase-iv-observational-study-and-subsequent-phase-ii-clinical-trial
#18
Ingrid Jakobsen Falk, Johan Lund, Henrik Gréen, Astrid Gruber, Evren Alici, Birgitta Lauri, Cecilie Blimark, Ulf-Henrik Mellqvist, Agneta Swedin, Karin Forsberg, Conny Carlsson, Mats Hardling, Lucia Ahlberg, Kourosh Lotfi, Hareth Nahi
PURPOSE: Despite therapeutic advances, patients with multiple myeloma (MM) continue to experience disease relapse and treatment resistance. The gene ABCB1 encodes the drug transporter P-glycoprotein, which confers resistance through drug extrusion across the cell membrane. Lenalidomide (Len) is excreted mainly via the kidneys, and, given the expression of P-gp in the renal tubuli, single-nucleotide polymorphisms (SNPs) in the ABCB1 gene may influence Len plasma concentrations and, subsequently, the outcome of treatment...
November 25, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29161704/long-term-renal-and-cardiac-outcomes-after-stenting-in-patients-with-resistant-hypertension-and-atherosclerotic-renal-artery-stenosis
#19
Cristiana Catena, GianLuca Colussi, Gabriele Brosolo, Nicolas Verheyen, Marileda Novello, Nicole Bertin, Alessandro Cavarape, Leonardo A Sechi
BACKGROUND/AIMS: Atherosclerotic renal artery stenosis (ARAS) is frequently detected in patients with resistant hypertension (RHTN), but the evidence supporting the utility of renal revascularization in these patients is limited. This prospective, observational study investigates the outcomes of renal stenting in patients with RHTN and hemodynamically significant ARAS. METHODS: Fifty-four patients with RHTN were selected because of angiographic evidence of ARAS >70% and were followed for 4 years after renal stenting...
2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29132351/therapeutic-efficacy-of-pentoxifylline-on-proteinuria-and-renal-progression-an-update
#20
REVIEW
Yung-Ming Chen, Wen-Chih Chiang, Shuei-Liong Lin, Tun-Jun Tsai
Blood pressure control with renin-angiotensin system (RAS) blockade has remained the gold standard for treating patients with proteinuric chronic kidney disease (CKD) up to date. Nevertheless, RAS blockade slows but does not halt the progression of kidney disease, thus highlighting the need to search for additional therapeutic approaches. The nonselective phosphodiesterase (PDE) inhibitor pentoxifylline (PTX) is an old drug that exhibits prominent anti-inflammatory, anti-proliferative and anti-fibrotic activities both in vitro and in vivo...
November 13, 2017: Journal of Biomedical Science
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