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Renal excretion of drugs

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https://www.readbyqxmd.com/read/28929659/-effects-and-mechanisms-of-shenkang-injection-promoting-extracellular-matrix-degradation-via-regulating-erk1-2-mmps-signaling-pathway-in-renal-failure-rats
#1
Jing-Jing Yang, Zhi-Min Mao, Yi-Gang Wan, Wei Wu, Yan-Ru Huang, Ge Shi, Wen-Bei Han, Jian Yao
This study aimed to clarify preliminarily the effects and mechanisms of Shenkang injection (SKI) promoting extracellular matrix(ECM)degradation via regulating extracellular-signal regulated protein kinase(ERK)1/2/matrix metalloproteinases(MMPs)signaling pathway in renal failure rats. Twenty rats were randomly divided into 4 groups:the Sham group,the Model group,the SKI group and the Enalapril maleate(EM)group. The model rats with renal failure were induced by intragastric administration of adenine and unilateral ureteral obstruction(UUO)...
October 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28926934/the-beneficial-effects-of-allicin-in-chronic-kidney-disease-are-comparable-to-losartan
#2
Ehécatl Miguel Ángel García Trejo, Abraham Said Arellano Buendía, Omegar Sánchez Reyes, Fernando Enrique García Arroyo, Raúl Arguello García, María Lilia Loredo Mendoza, Edilia Tapia, Laura Gabriela Sánchez Lozada, Horacio Osorio Alonso
Recent studies suggest that allicin may play a role in chronic kidney disease (CKD), reducing hypertension and oxidative stress and improving renal dysfunction. In the present study, CKD was induced by 5/6 nephrectomy and the animals were divided into four treatment groups as follows: control (C), CKD, CKD+allicin (40 mg/kg pathway oral) (CKDA), and CKD+Losartan (20 mg/kg) (CKDL). After CKD induction, the rats developed hypertension from week 3 to the end of the study. This was associated with increased creatinine and blood urea nitrogen (BUN) levels in serum, increased albuminuria, increased urinary excretion of N-acetyl-β-d-glucosaminidase (NAG), increased nephrin expression, and incrased histological alterations in the cortex...
September 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28904428/collapsing-glomerulopathy-a-troublemaker-for-the-renal-allograft-lessons-learnt
#3
K V Kanodia, A V Vanikar, L K Nigam, R D Patel, K S Suthar, H V Patel, H L Trivedi
Collapsing glomerulopathy (CG) is a well-recognized distinct morphological pattern of proliferative parenchymal injury leading to rapid graft failure. We conducted a single-center retrospective study to evaluate the prevalence, clinicopathological features, and prognosis of CG in renal transplant recepient. We analyzed 2518 renal allograft biopsies performed from 2007 to 2015 and correlated their clinicopathological features. The prevalence of CG was 0.83% (21 out of 2518) of allograft biopsies with a higher prevalence of 1...
September 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28902176/pharmacokinetic-and-toxicodynamic-characterization-of-a-novel-doxorubicin-derivative
#4
Samaa Alrushaid, Casey L Sayre, Jaime A Yáñez, M Laird Forrest, Sanjeewa N Senadheera, Frank J Burczynski, Raimar Löbenberg, Neal M Davies
Doxorubicin (Dox) is an effective anti-cancer medication with poor oral bioavailability and systemic toxicities. DoxQ was developed by conjugating Dox to the lymphatically absorbed antioxidant quercetin to improve Dox's bioavailability and tolerability. The purpose of this study was to characterize the pharmacokinetics and safety of Dox after intravenous (IV) and oral (PO) administration of DoxQ or Dox (10 mg/kg) and investigate the intestinal lymphatic delivery of Dox after PO DoxQ administration in male Sprague-Dawley rats...
September 13, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28883395/bio-degradable-highly-fluorescent-conjugated-polymer-nanoparticles-for-bio-medical-imaging-applications
#5
Tatjana Repenko, Anne Rix, Simon Ludwanowski, Dennis Go, Fabian Kiessling, Wiltrud Lederle, Alexander J C Kuehne
Conjugated polymer nanoparticles exhibit strong fluorescence and have been applied for biological fluorescence imaging in cell culture and in small animals. However, conjugated polymer particles are hydrophobic and often chemically inert materials with diameters ranging from below 50 nm to several microns. As such, conjugated polymer nanoparticles cannot be excreted through the renal system. This drawback has prevented their application for clinical bio-medical imaging. Here, we present fully conjugated polymer nanoparticles based on imidazole units...
September 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28867717/effects-of-tripterygium-wilfordii-hook-f-induction-therapy-to-iga-nephropathy-patients-with-heavy-proteinuria
#6
Zhen Wang, Chao Yu, Li-Na Zhou, Xin Chen
Although some new drugs have been developed, Tripterygium wilfordii Hook F.(TWHF)has the merits of relatively lower price and fewer side effects. Unfortunately, the efficacy and safety of the TWHF (especially dosage 120mg/day) in the IgA nephropathy(IgAN) are still lacking. A cohort study including 49 IgAN patients with heavy proteinuria who received induction therapy was undertaken. Patients were divided into three groups: Prednisone (PRE), conventional-dose TWHF (CTW) and double-dose TWHF (DTW). The clinical features, laboratory data, histological manifestations and outcomes of the groups were compared...
September 1, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28861952/use-of-sodium-glucose-cotransporter%C3%A2-2-inhibitors-in-older-patients-with-type%C3%A2-2-diabetes-mellitus
#7
Takahiro Kambara, Rei Shibata, Hiroyuki Osanai, Yoshihito Nakashima, Hiroshi Asano, Kazuyoshi Sakai, Toyoaki Murohara, Masayoshi Ajioka
AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic agents that act on the proximal renal tubules to lower blood glucose levels by inhibiting glucose reabsorption and promoting urinary glucose excretion. The present study assessed the long-term use of SGLT2 inhibitors in older patients with diabetes. METHODS: A total of 117 older patients with type 2 diabetes who were given SGLT2 inhibitors were enrolled from April 2014 to March 2016. RESULTS: The mean age of the patients was 73...
September 1, 2017: Geriatrics & Gerontology International
https://www.readbyqxmd.com/read/28846728/carbon-nanotubes-exhibit-fibrillar-pharmacology-in-primates
#8
Simone Alidori, Daniel L J Thorek, Bradley J Beattie, David Ulmert, Bryan Aristega Almeida, Sebastien Monette, David A Scheinberg, Michael R McDevitt
Nanomedicine rests at the nexus of medicine, bioengineering, and biology with great potential for improving health through innovation and development of new drugs and devices. Carbon nanotubes are an example of a fibrillar nanomaterial poised to translate into medical practice. The leading candidate material in this class is ammonium-functionalized carbon nanotubes (fCNT) that exhibits unexpected pharmacological behavior in vivo with important biotechnology applications. Here, we provide a multi-organ evaluation of the distribution, uptake and processing of fCNT in nonhuman primates using quantitative whole body positron emission tomography (PET), compartmental modeling of pharmacokinetic data, serum biomarkers and ex vivo pathology investigation...
2017: PloS One
https://www.readbyqxmd.com/read/28845946/-nephrolithiasis-coexisting-with-type-2-diabetes-current-concept-of-the-features-of-stone-formation-and-the-effects-of-hypoglycemic-therapy-on-lithogenesis
#9
S K Yarovoi, S A Golovanov, M R Khaziakhmetova, O V Dzhalilov
The article analyzes Russian and international literature examining specific features of the pathogenesis of renal stones in the setting of carbohydrate metabolism disorders. The authors outline the renal effects of the main pharmacological groups of oral hypoglycemic drugs regarding metaphylaxis of nephrolithiasis. An increased risk of nephrolithiasis in type 2 diabetes mellitus is realized through hyperuricemia with concurrent urine acidification. Current literature is lacking studies on the effects of oral hypoglycemic drugs on urine properties...
July 2017: Urologii︠a︡
https://www.readbyqxmd.com/read/28836175/canagliflozin-a-review-in-type-2-diabetes
#10
Emma D Deeks, André J Scheen
Canagliflozin (Invokana(®)) is a sodium-glucose co-transporter-2 (SGLT2) inhibitor indicated in various countries worldwide for the once-daily oral treatment of type 2 diabetes (T2D). Canagliflozin lowers blood glucose levels independently of insulin, with the inhibition of SGLT2 reducing renal reabsorption of glucose and increasing excretion of glucose in the urine. In well-designed clinical trials, canagliflozin (as first-line monotherapy or add-on therapy to other antihyperglycaemic agents) improved glycaemic control in adults with T2D, including those of older age and/or at high cardiovascular (CV) risk, and also had beneficial effects on their bodyweight and blood pressure (BP)...
August 23, 2017: Drugs
https://www.readbyqxmd.com/read/28820069/apixaban-effective-and-safe-in-preventing-thromboembolic-events-in-patients-with-atrial-fibrillation-and-renal-failure
#11
Francesca Cortese, Pietro Scicchitano, Michele Gesualdo, Gabriella Ricci, Santa Carbonara, Carlo Franchini, Brigida Immacolata Pia Schiavone, Filomena Corbo, Marco Matteo Ciccone
Thromboembolic events, principally stroke, represent among the leading causes of morbidity and mortality of subjects with atrial fibrillation, with an incidence about 5 times higher compared to healthy subjects. Chronic kidney disease, frequently associated with atrial fibrillation, determines itself a further increase of thromboembolic events, bleeding and mortality. In addition, the presence of renal failure complicates the pharmacological management of these patients, mainly due to the side effects of antiarrhythmic and anticoagulant drugs with renal excretion, due to their accumulation...
August 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28808888/has-time-come-for-the-use-of-direct-oral-anticoagulants-in-the-extended-prophylaxis-of-venous-thromboembolism-in-acutely-ill-medical-patients-yes
#12
Walter Ageno
Betrixaban is a direct factor Xa inhibitor with a renal excretion of only approximately 5-7%. On June 23rd 2017, it became the first direct oral anticoagulant to receive Food and Drug Administration approval for the prevention of venous thromboembolism in acutely ill medical patients, and the first anticoagulant agent to be approved for extended-duration thromboprophylaxis after hospital discharge in this setting. Approval followed the results of the APEX trial, a phase III clinical trial comparing betrixaban (80 mg) administered for 35-42 days with enoxaparin (40 mg) administered for 10 ± 4 days...
August 14, 2017: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/28805977/prevention-against-renal-damage-in-rats-with-subtotal-nephrectomy-by-sacubitril-valsartan-lcz696-a-dual-acting-angiotensin-receptor-neprilysin-inhibitor
#13
Kentaro Ushijima, Hitoshi Ando, Yusuke Arakawa, Kenichi Aizawa, Chisato Suzuki, Ken Shimada, Shu-Ichi Tsuruoka, Akio Fujimura
Although patients with chronic kidney disease (CKD) are at increased risk for end-stage renal disease and cardiovascular events, adequate drug therapies for preventing the deterioration of these conditions are still not established. This study was undertaken to evaluate a preventive effect of an angiotensin receptor-neprilysin inhibitor sacubitril/valsartan (LCZ696), which is converted to sacubitril and valsartan in the body, against the progression of renal disease in rats with subtotal nephrectomy, an animal model of human CKD...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28790147/hepatocyte-specific-deletion-of-egfr-in-mice-reduces-hepatic-abcg2-transport-activity-measured-with-11-c-erlotinib-and-positron-emission-tomography
#14
Alexander Traxl, Karin Komposch, Elisabeth Glitzner, Thomas Wanek, Severin Mairinger, Oliver Langer, Maria Sibilia
The epidermal growth factor receptor (EGFR) regulates cellular expression levels of breast cancer resistance protein (humans: ABCG2, rodents: Abcg2) via its downstream signaling pathways. Drugs that inhibit EGFR signaling (e.g. tyrosine kinase inhibitors, antibodies) may lead to ABCG2-mediated drug-drug interactions (DDIs) by changing disposition of concomitantly administered ABCG2 substrate drugs. In this study we used positron emission tomography (PET)/magnetic resonance (MR) imaging to compare disposition of the model Abcg2 substrate [(11)C]erlotinib in a mouse model of hepatocyte-specific deletion of EGFR (EGFR(Δhep) mice, n = 5) with EGFR(fl/fl) control mice (n = 6), which have normal EGFR expression levels in all tissues...
August 8, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28779862/neurological-complications-of-renal-disease
#15
Jorge H Baluarte
Neurological manifestations related to electrolyte disorders, drug toxicity, and uremia are common in chronic kidney disease (CKD). Seizures and coma are frequent complications of acute renal insufficiency (uremia), whereas peripheral neuropathy and encephalopathy, observed in progressive uremia, are terminal events. Failure to excrete metabolic products causes their accumulation and can lead to severe intoxication. Clinically, the signs and symptoms of uremia can vary widely, depending on the biological characteristics of the patient, the specific type of renal disease, and the time of the uremic intoxication...
February 2017: Seminars in Pediatric Neurology
https://www.readbyqxmd.com/read/28767098/chemical-modifications-of-nucleic-acid-aptamers-for-therapeutic-purposes
#16
REVIEW
Shuaijian Ni, Houzong Yao, Lili Wang, Jun Lu, Feng Jiang, Aiping Lu, Ge Zhang
Nucleic acid aptamers have minimal immunogenicity, high chemical synthesis production, low cost and high chemical stability when compared with antibodies. However, the susceptibility to nuclease degradation, rapid excretion through renal filtration and insufficient binding affinity hindered their development as drug candidates for therapeutic applications. In this review, we will discuss methods to conquer these challenges and highlight recent developments of chemical modifications and technological advances that may enable early aptamers to be translated into clinical therapeutics...
August 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28760226/positioning-of-sodium-glucose-cotransporter-2-inhibitors-in-national-and-international-guidelines
#17
Carlos Morillas
Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) selectively and reversibly inhibit sodium-glucose cotransporter-2 (SGLT2), promoting renal glucose excretion and reducing plasma glycaemia. By increasing renal glucose excretion, these drugs favour a negative energy balance, leading to weight loss. Their glucoselowering effect is independent of insulin. Although these drugs have only recently been developed, they have been included in all the main national and international guidelines since 2014. The present review summarises the most important recommendations on the use of SGLT2 in patients with DM2 contained in the most recently published guidelines and consensus statements...
November 2016: Medicina Clínica
https://www.readbyqxmd.com/read/28756612/clinical-pharmacokinetics-of-systemically-administered-antileishmanial-drugs
#18
REVIEW
Anke E Kip, Jan H M Schellens, Jos H Beijnen, Thomas P C Dorlo
This review describes the pharmacokinetic properties of the systemically administered antileishmanial drugs pentavalent antimony, paromomycin, pentamidine, miltefosine and amphotericin B (AMB), including their absorption, distribution, metabolism and excretion and potential drug-drug interactions. This overview provides an understanding of their clinical pharmacokinetics, which could assist in rationalising and optimising treatment regimens, especially in combining multiple antileishmanial drugs in an attempt to increase efficacy and shorten treatment duration...
July 29, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28753040/evaluation-of-sofosbuvir-velpatasvir-plus-voxilaprevir-as-fixed-dose-co-formulation-for-treating-hepatitis-c
#19
Vicente Soriano, Laura Benítez-Gutiérrez, Ana Arias, Itziar Carrasco, Pablo Barreiro, Jose M Peña, Carmen de Mendoza
The fixed-dose combination of three direct-acting antivirals (DAA), namely sofosbuvir, velpatasvir and voxilaprevir is the first pangenotypic, single tablet regimen developed for the treatment of HCV infection. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy and safety of the co-formulation are reviewed. Information on drug absorption, distribution, metabolism and excretion of each of the three antivirals is evaluated. Finally, antiviral activity, safety and potential for drug interactions in phase II/III clinical trials in distinct patient populations are discussed...
July 28, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28750560/pharmacokinetic-drug-evaluation-of-lacosamide-for-the-treatment-of-partial-onset-seizures
#20
Stefano de Biase, Mariarosaria Valente, Gian Luigi Gigli, Giovanni Merlino
The goal of pharmacologic therapy with antiepileptic drugs (AEDs) is to reduce the frequency of seizures and achieve a seizure-free state with minimal side effects. However 30% of patients treated with available AEDs continue to experience uncontrolled seizures. There is still need for new AEDs with enhanced effectiveness and tolerability. Areas covered: The present manuscript is based on an extensive Internet and PubMed search from 1992 to 2017. It is focused on the pharmacokinetic properties of lacosamide (LCM) for the treatment of partial-onset seizures...
July 30, 2017: Expert Opinion on Drug Metabolism & Toxicology
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