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Renal excretion of drugs

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https://www.readbyqxmd.com/read/28724202/population-pharmacokinetics-of-lenalidomide-in-healthy-volunteers-and-patients-with-hematologic-malignancies
#1
Jamie N Connarn, Renfang Hwang, Yue Gao, Maria Palmisano, Nianhang Chen
A population pharmacokinetic (PopPK) model of lenalidomide was developed using data pooled from 13 clinical studies (dose range, 5-400 mg) in participants who were considered to have adequate capability for renal excretion of lenalidomide (creatinine clearance [CrCl] > 50 mL/min). The analysis population included 305 healthy volunteers and 83 patients with multiple myeloma or myelodysplastic syndromes. A 1-compartment model with linear absorption and elimination described well the observed data for both healthy volunteers and patients...
July 19, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28721043/preparation-of-exenatide-loaded-linear-poly-ethylene-glycol-brush-poly-l-lysine-block-copolymer-potential-implications-on-diabetic-nephropathy
#2
Fei Tong
The poly(ethylene glycol)-b-brush poly(l-lysine) polymer (PEG-b-(PELG50-g-PLL3)) was synthesized and evaluated as a nanocarrier for prolonging delivery of exenatide through the abdominal subcutaneous injection route. The isoelectric point of exenatide was 4.86, and exenatide could combine with PEG-b-(PELG50-g-PLL3) polymers via electrostatic interactions at pH 7.4. This polymer was a good candidate for achieving prolonged drug delivery for exenatide, considering its high molecular weight. Besides the physicochemical characterization of the polymer, in vitro and in vivo applications were researched as a sustained exenatide delivery system...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28719008/comparative-efficacy-and-safety-of-gemigliptin-versus-linagliptin-in-type-2-diabetes-patients-with-renal-impairment-a-40-week-extension-of-the-guard-randomized-study
#3
Sang Youb Han, Sun Ae Yoon, Byoung Geun Han, Sung Gyun Kim, Young-Il Jo, Kyung Hwan Jeong, Kook-Hwan Oh, Hyeong Cheon Park, Sun-Hee Park, Shin-Wook Kang, Ki-Ryang Na, Sun Woo Kang, Nam-Ho Kim, Younghwan Jang, Bogyeong Kim, Seonghye Shin, Dae Ryong Cha
AIMS: The present extension study evaluated the long-term safety and efficacy of gemigliptin during a 40-week follow-up period after a 12-week study. METHODS: The main study was a randomized, placebo-controlled, double-blinded, phase IIIb study in which 50 mg of gemigliptin (N = 66) or placebo (N = 66) was administered to patients with type 2 diabetes mellitus (T2DM) with moderate or severe renal impairment over a 12-week period. Patients with a glycated haemoglobin (HbA1c) level of 7-11% and an estimated glomerular filtration rate (eGFR) of 15-59 mL/min/1...
July 18, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28714036/pharmacokinetics-of-intravenous-pan-class-i-phosphatidylinositol-3-kinase-pi3k-inhibitor-14-c-copanlisib-bay-80-6946-in-a-mass-balance-study-in-healthy-male-volunteers
#4
Michael Gerisch, Thomas Schwarz, Dieter Lang, Gabriele Rohde, Stefanie Reif, Isabelle Genvresse, Susanne Reschke, Dorina van der Mey, Camille Granvil
PURPOSE: To determine the pharmacokinetics of radiolabeled copanlisib (BAY 80-6946) in healthy male volunteers and to investigate the disposition and biotransformation of copanlisib. METHODS: A single dose of 12 mg copanlisib containing 2.76 MBq [(14)C]copanlisib was administered as a 1-h intravenous infusion to 6 volunteers with subsequent sampling up to 34 days. Blood, plasma, urine and feces were collected to monitor total radioactivity, parent compound and metabolites...
July 11, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28689437/the-effect-of-antiepileptic-drugs-on-the-kidney-function-and-structure
#5
S Hamed
Abtract Introduction: Long-term use of antiepileptic drugs (AEDs) is associated with number of somatic conditions. Data from experimental, cross-sectional and prospective studies have evidence for the deleterious effect of some AEDs on the kidney. Areas Covered: This review summarized the current knowledge of the effect of AEDs on the kidney including evidence and mechanisms. Fanconi syndrome was reported with valproate (VPA) therapy in severely disabled children with epilepsy. Renal tubular acidosis and urolithiasis were reported with acetazolamide, topirmate and zonisamide, drugs with carbonic anhydrase inhibition properties...
July 10, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28685934/does-sglt2-inhibition-with-dapagliflozin-overcome-individual-therapy-resistance-to-raas-inhibition
#6
Sergei Petrykiv, Goos Laverman, Dick de Zeeuw, Hiddo J L Heerspink
AIMS: Individual patients show a large variation in their response to renin-angiotensin-aldosteron-system blockade both in surrogates like albuminuria and hard renal outcomes. Sodium-glucose co-transporter 2 inhibitors (SGLT2) have been shown to lower albuminuria and to confer cardiovascular and possibly renal protection. To establish whether individual therapy resistance to RAASi can be overcome by adding an SGLT2 inhibitor we assessed individual albuminuria responses in patients exposed both to RAASi and the SGLT2 inhibitor dapagliflozin...
July 7, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28684123/aspirin-and-blood-pressure-effects-when-used-alone-or-in-combination-with-antihypertensive-drugs
#7
REVIEW
Ana Catarina Costa, Marta Reina-Couto, António Albino-Teixeira, Teresa Sousa
Arterial hypertension is a major risk factor for cardiovascular and renal events. Lowering blood pressure is thus an important strategy for reducing morbidity and mortality. Since low-dose aspirin is a cornerstone in the prevention of adverse cardiovascular outcomes, combined treatment with aspirin and antihypertensive drugs is very common. However, the impact of aspirin therapy on blood pressure control remains a subject of intense debate. Recent data suggest that the cardioprotective action of aspirin extends beyond its well-known antithrombotic effect...
July 3, 2017: Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology
https://www.readbyqxmd.com/read/28679591/greater-transforming-growth-factor-%C3%AE-in-adult-female-shr-is-dependent-on-blood-pressure-but-does-not-account-for-sex-differences-in-renal-t-regulatory-cells
#8
Ashlee J Tipton, Jacqueline B Musall, G Ryan Crislip, Jennifer C Sullivan
Female spontaneously hypertensive rats (SHR) have more renal regulatory T cells (Tregs) than males, and greater levels of Tregs in female SHR is dependent on blood pressure (BP). However, the molecular mechanism responsible for greater Tregs in female SHR is unknown. Transforming growth factor (TGF)-β is a pleiotropic cytokine critical in the differentiation of naïve T cells into Tregs, and female SHR have higher TGF-β excretion than male SHR. The goals of the current study were to test the hypotheses that 1) female SHR have greater renal TGF-β expression than male SHR which is dependent on BP and 2) neutralizing TGF-β will decrease renal Tregs in female SHR...
July 5, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28670881/ameliorative-effect-of-coenzyme-q10-and-or-candesartan-on-carboplatin-induced-nephrotoxicity-roles-of-apoptosis-transforming-growth-factor-%C3%AE-1-nuclear-factor-kappa-b-and-the-nrf2-ho-1-pathway
#9
Ahmed M Kabel, Abeer A Elkhoely
Background: Carboplatin is a drug that is used for treatment of many types of cancer. However, it may produce serious nephrotoxicity. Candesartan is angiotensin II receptor antagonist employed mainly for control of hypertension. Coenzyme Q10 (CoQ10) is a fat-soluble substance which was proven to have potent antioxidant and anti-inflammatory properties. Aim: Our aim was to study the effects of candesartan and/or CoQ10 on carboplatin-induced nephrotoxicity in mice. Methods: Sixty mice were divided into 6 equal groups: Control untreated; carboplatin; carboplatin + candesartan; carboplatin + CoQ10; carboplatin + carboxymethyl cellulose; and carboplatin + candesartan + CoQ10 group...
June 25, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28667460/prediction-of-the-effect-of-renal-impairment-on-the-pharmacokinetics-of-new-drugs
#10
Elisa Borella, Italo Poggesi, Paolo Magni
INTRODUCTION: Renal impairment may have a significant impact on the pharmacokinetics of drugs. Ad hoc studies in subjects with renal impairment are required by the regulatory authorities to propose dose adjustments in these subjects, to find a dosing regimen able to provide a systemic exposure similar to those in subjects with a normal renal function given the relevant clinical dose. METHODS: To evaluate the main descriptors and establish a predictive model of the effect of renal impairment on the exposure of new drugs, we considered 73 marketed drugs, for which studies in subjects with different degrees of renal impairment were available in the literature...
June 30, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28667064/disposition-and-clinical-implications-of-protein-bound-uremic-toxins
#11
REVIEW
Jitske Jansen, Joachim Jankowski, Prathibha R Gajjala, Jack F M Wetzels, Rosalinde Masereeuw
In patients with chronic kidney disease (CKD), adequate renal clearance is compromised, resulting in the accumulation of a plethora of uremic solutes. These uremic retention solutes, also named uremic toxins, are a heterogeneous group of organic compounds with intrinsic biological activities, many of which are too large to be filtered and/or are protein bound. The renal excretion of protein-bound toxins depends largely on active tubular secretion, which shifts the binding and allows for active secretion of the free fraction...
July 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28665228/absorption-metabolism-and-excretion-of-14-c-omarigliptin-a-once-weekly-dpp-4-inhibitor-in-humans
#12
Shiyao Xu, Dan Tatosian, Ian Mcintosh, Maria Caceres, Catherine Matthews, Koppara Samuel, Diana Selverian, Sanjeev Kumar, Eunkyung Kauh
1. Omarigliptin (MARIZEV®) is a once-weekly DPP-4 inhibitor approved in Japan for the treatment of type 2 diabetes. The objective of this study was to investigate the absorption, metabolism and excretion of omarigliptin in humans. 2. Six healthy subjects received a single oral dose of 25 mg (2.1 µCi) [(14)C]omarigliptin. Blood, plasma, urine and fecal samples were collected at various intervals for up to 20 days post-dose. Radioactivity levels in excreta and plasma/blood samples were determined by accelerator mass spectrometry (AMS)...
June 30, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28656379/physiology-and-pathophysiology-of-the-plasminogen-system-in-the-kidney
#13
REVIEW
Per Svenningsen, Gitte Rye Hinrichs, Rikke Zachar, Rikke Ydegaard, Boye L Jensen
The plasminogen system is important for fibrinolysis in addition to tissue remodeling and inflammation with significance for kidney disease. The system consists of the circulating zymogen plasminogen (Plg) and the tissue- and urokinase-type plasminogen activators, tPA and uPA, expressed in the glomeruli, endothelium and tubular epithelium, respectively, and the inhibitors α2-antiplasmin and plasminogen activator inhibitor-type1, PAI-1. Plasminogen is activated by surface receptors, some with renal expression: urokinase-type plasminogen activator receptor (uPAR), plasminogen receptor KT (Plg-RKT), and tPA, most evident in the endothelium...
June 27, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28653271/regadenoson-use-in-chronic-kidney-disease-and-end-stage-renal-disease-a-focused-review
#14
Aviral Vij, Yasmeen Golzar, Rami Doukky
Regadenoson is a selective A2A adenosine receptor agonist that has been approved as a vasodilator stress agent with single-photon emission-computed tomography (SPECT) myocardial perfusion imaging (MPI). Since its approval by the Food and Drug Administration (FDA) in 2008, it has become the most commonly used pharmacologic stress agent with SPECT-MPI. Given that it is predominantly renally excreted, its use in patients with chronic kidney disease has been the subject of active post-marketing clinical research...
June 26, 2017: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
https://www.readbyqxmd.com/read/28649076/renal-clearance-and-urinary-excretion-of-omeprazole-in-healthy-female-volunteers-in-pakistan
#15
Nazia Qadir, Tanweer Khaliq, Rai Altaf Hussain, Ghulam Abbas Shah, Sadia Asharaf, Ahmad Raza, Nadia Noor
Omeprazole is a widely prescribed proton pump inhibitor to treat various gastric acid hyper secretion disorders. The present study was designed to evaluate the renal clearance and urinary excretion of omeprazole in eight healthy female volunteers to increase the understanding of the contributing factors such as demographics variability in the renal clearance and urinary excretion of omeprazole under indigenous conditions. The urine and blood samples were collected 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours after oral administration of enteric coated omeprazole (20 mg) and drug concentration in the samples was determined by High Performance Liquid Chromatography (HPLC) with C18 column and UV detector...
March 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28648206/how-to-assess-the-efficacy-of-phosphate-binders
#16
Francisco Caravaca, Fernando Caravaca-Fontán, Lilia Azevedo, Enrique Luna
BACKGROUND AND AIMS: The efficacy of phosphate binders is difficult to be estimated clinically. This study analyzes the changes in serum phosphate and urinary phosphate excretion after the prescription of phosphate binders (PB) in patients with chronic kidney disease stage 4-5 pre-dialysis, and the usefulness of the ratio between total urinary phosphate and protein catabolic rate (Pu/PCR) for estimating the efficacy of PB. METHODS: This retrospective observational cohort study included adult chronic kidney disease patients...
May 2017: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/28640195/pharmacogenomic-variants-may-influence-the-urinary-excretion-of-novel-kidney-injury-biomarkers-in-patients-receiving-cisplatin
#17
Cara Chang, Yichun Hu, Susan L Hogan, Nickie Mercke, Madeleine Gomez, Cindy O'Bryant, Daniel W Bowles, Blessy George, Xia Wen, Lauren M Aleksunes, Melanie S Joy
Nephrotoxicity is a dose limiting side effect associated with the use of cisplatin in the treatment of solid tumors. The degree of nephrotoxicity is dictated by the selective accumulation of cisplatin in renal tubule cells due to: (1) uptake by organic cation transporter 2 (OCT2) and copper transporter 1 (CTR1); (2) metabolism by glutathione S-transferases (GSTs) and γ-glutamyltransferase 1 (GGT1); and (3) efflux by multidrug resistance-associated protein 2 (MRP2) and multidrug and toxin extrusion protein 1 (MATE1)...
June 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28634536/telavancin-a-novel-semisynthetic-lipoglycopeptide-agent-to-counter-the-challenge-of-resistant-gram-positive-pathogens
#18
REVIEW
Biswadeep Das, Chayna Sarkar, Debasmita Das, Amit Gupta, Arnav Kalra, Shubham Sahni
Telavancin (TD-6424), a semisynthetic lipoglycopeptide vancomycin-derivative, is a novel antimicrobial agent developed by Theravance for overcoming resistant Gram-positive bacterial infections, specifically methicillin-resistant Staphylococcus aureus (MRSA). The US Food and Drug Administration (USFDA) had approved telavancin in 2009 for the treatment of complicated skin and skin structure infections (cSSSIs) caused by Gram-positive bacteria, including MRSA (S. aureus, Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus anginosus group, or Enterococcus faecalis)...
March 2017: Therapeutic Advances in Infectious Disease
https://www.readbyqxmd.com/read/28625368/effect-of-aspirin-on-renal-disease-progression-in-patients-with-type-2-diabetes-a-multicenter-double-blind-placebo-controlled-randomized-trial-the-renal-disease-progression-by-aspirin-in-diabetic-patients-leda-trial-rationale-and-study-design
#19
Francesco Violi, Giovanni Targher, Annarita Vestri, Roberto Carnevale, Maurizio Averna, Alessio Farcomeni, Andrea Lenzi, Francesco Angelico, Francesco Cipollone, Daniele Pastori
Type 2 diabetes mellitus (T2DM) is one of the most common causes of chronic kidney disease and kidney failure. It has been estimated that the annual decline of estimated glomerular filtration rate (eGFR) among patients with T2DM is approximately 2.0-2.5mL min(-1) y(-1). Cyclooxygenase-dependent eicosanoids, such as 11-dehydro-thromboxane (Tx)B2, are increased in T2DM patients and are potentially involved in the regulation of renal blood flow. Animal models showed that cyclooxygenase inhibitors, such as aspirin, are associated with improvements in renal plasma flow and eGFR values...
July 2017: American Heart Journal
https://www.readbyqxmd.com/read/28615947/treatment-of-secondary-hyperparathyroidism-the-clinical-utility-of-etelcalcetide
#20
REVIEW
Mario Cozzolino, Andrea Galassi, Ferruccio Conte, Michela Mangano, Luca Di Lullo, Antonio Bellasi
Secondary hyperparathyroidism (SHPT), a very frequent, severe, and worsening complication of chronic kidney disease, is characterized by high serum parathyroid hormone (PTH), parathyroid gland hyperplasia, and disturbances in mineral metabolism. Clinically, SHPT shows renal osteodystrophy, vascular calcification, cardiovascular damage, and fatal outcome. Calcium-sensing receptor (CaSR) is the main physiological regulator of PTH secretion; its activation by calcium rapidly inhibits PTH. Another important player in regulating mineral metabolism is vitamin D receptor (VDR), which is under the influence of vitamin D and influences the intestinal absorption of calcium and phosphate, PTH gene expression, and bone calcium mobilization...
2017: Therapeutics and Clinical Risk Management
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