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Renal excretion of drugs

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https://www.readbyqxmd.com/read/27906418/assessment-of-celecoxib-poly-lactic-co-glycolic-acid-nanoformulation-on-drug-pharmacodynamics-and-pharmacokinetics-in-rats
#1
S Harirforoosh, K O West, D E Murrell, J W Denham, P C Panus, G A Hanley
OBJECTIVE:  Celecoxib (CEL) is a nonsteroidal anti-inflammatory drug (NSAID) showing selective cycloxygenase-2 inhibition. While effective as a pain reducer, CEL exerts some negative influence on renal and gastrointestinal parameters. This study examined CEL pharmacodynamics and pharmacokinetics following drug reformulation as a poly(lactic-co-glycolic) acid nanoparticle (NP). MATERIALS AND METHODS: Rats were administered either vehicle (VEH) (methylcellulose solution), blank NP, 40 mg/kg CEL in methylcellulose, or an equivalent NP dose (CEL-NP)...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27878313/targeting-renal-glucose-reabsorption-to-treat-hyperglycaemia-the-pleiotropic-effects-of-sglt2-inhibition
#2
REVIEW
Volker Vallon, Scott C Thomson
Healthy kidneys filter ∼160 g/day of glucose (∼30% of daily energy intake) under euglycaemic conditions. To prevent valuable energy from being lost in the urine, the proximal tubule avidly reabsorbs filtered glucose up to a limit of ∼450 g/day. When blood glucose levels increase to the point that the filtered load exceeds this limit, the surplus is excreted in the urine. Thus, the kidney provides a safety valve that can prevent extreme hyperglycaemia as long as glomerular filtration is maintained. Most of the capacity for renal glucose reabsorption is provided by sodium glucose cotransporter (SGLT) 2 in the early proximal tubule...
November 22, 2016: Diabetologia
https://www.readbyqxmd.com/read/27862213/synthesis-and-preliminary-biological-evaluation-of-a-99m-tc-chlorambucil-derivative-as-a-potential-tumor-imaging-agent
#3
Jianguo Lin, Ling Qiu, Gaochao Lv, Ke Li, Wei Wang, Guiqing Liu, Xueyu Zhao, Shanshan Wang
Technetium-99 m-based radiopharmaceuticals have been used widely as diagnostic agents in the nuclear medicine. Chlorambucil (CLB) as one typical alkylating drug exhibits excellent inhibition effects against many human malignancies. In order to develop and explore a novel potential imaging agent for early diagnosis of tumors, tricarbonyl technetium-99 m and rhenium complexes based on the tridentate ligand dipicolylamine (DPA) bound to the chlorambucil pharmacophore were designed and synthesized: (99m) Tc-DPA-CLB (3) and Re-DPA-CLB (4)...
November 16, 2016: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/27860049/pimpinella-anisum-l-ethanolic-extract-ameliorates-the-gentamicin-induced-nephrotoxicity-in-rats
#4
Saeed Changizi-Ashtiyani, Amirhassan Seddigh, Houshang Najafi, Nasser Hossaini, Amir Avan, Ahmad Akbary, Mostafa Manian, Reza Nedaeinia
AIM: Gentamicin (GM) is one of the commonest causes of drug-induced nephrotoxicity. Moreover, oxidative stress plays an important role in gentamicin-induced nephrotoxicity. The current study aimed to explore the anti-oxidant and protective effects of Pimpinella anisum (P. anisum) on the alleviation of GM-induced damage. METHODS: Forty male wistar rats were divided into four groups: control, sham that was administrated normal saline orally and intraperitoneally (i...
November 8, 2016: Nephrology
https://www.readbyqxmd.com/read/27855567/pradigastat-disposition-in-humans-in-vivo-and-in-vitro-investigations
#5
Alana Upthagrove, Jin Chen, Charles D Meyers, Kenneth Kulmatycki, Angela Bretz, Lai Wang, Lana Peng, Safet Palamar, Melissa Lin, Tapan Majumdar, Phi Tran, Heidi J Einolf
1. Pradigastat is a potent and specific diacylglycerol acyltransferase-1 (DGAT1) inhibitor effective in lowering postprandial triglycerides in healthy human subjects and fasting triglycerides in familial chylomicronemia syndrome (FCS) patients. 2. Here we present the results of human oral absorption, metabolism and excretion (AME), intravenous pharmacokinetic (PK), and in vitro studies which together provide an overall understanding of the disposition of pradigastat in humans. 3. In human in vitro systems, pradigastat is metabolized slowly to a stable acyl glucuronide (M18...
November 18, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27854055/fixed-dose-combination-of-canagliflozin-and-metformin-for-the-treatment-of-type-2-diabetes-an-overview
#6
REVIEW
Jaime A Davidson, Lance Sloan
: Metformin is recommended as a first-line therapy for patients with type 2 diabetes mellitus (T2DM). However, many patients do not achieve glycemic goals with metformin monotherapy and require subsequent combination therapy with other antihyperglycemic agents (AHAs). For newly diagnosed patients with high blood glucose, initial combination therapy may be required to achieve glycemic control. The American Association for Clinical Endocrinologists algorithm for the treatment of T2DM recommends metformin plus a sodium glucose co-transporter 2 (SGLT2) inhibitor as the first oral combination in patients who present with HbA1c ≥7...
November 16, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27843635/renal-insufficiency-and-cancer-treatments
#7
REVIEW
Vincent Launay-Vacher, Nicolas Janus, Gilbert Deray
Renal insufficiency has been shown to be highly prevalent in patients with cancer. This renal insufficiency has been reported to be associated with reduced overall survival and increased cancer-related mortality. Therefore, it is important to screen patients with cancer for renal insufficiency, using an adequate and reliable method of estimation of the renal function. Renal insufficiency may influence 1 or several of the 4 pharmacokinetic phases (absorption, distribution, metabolism, elimination/excretion), potentially resulting in marked modifications of the pharmacokinetic profile of a drug in patients with renal insufficiency...
2016: ESMO Open
https://www.readbyqxmd.com/read/27817253/multidrug-and-toxin-extrusion-protein-1-mediated-interaction-of-metformin-and-scutellariae-radix-in-rats
#8
Sreymom Yim, Byoung Hoon You, Hee-Sung Chae, Young-Won Chin, Hojun Kim, Han Seok Choi, Young Hee Choi
The metformin and Scutellariae Radix extract (SB) combination has been previously reported to enhance anti-diabetic activity. Considering that organic cation transporters (OCTs) and multi-drug and toxin extrusion proteins (MATEs) in the liver and kidney are determinant factors on hepatic distribution and renal clearance of metformin, the effects of SB on OCT or MATE-mediated systemic exposure of metformin as well as on glucose tolerance and hypoglycemia were examined. Although SB inhibited metformin uptake through human transporters OCT1 and MATE1 in vitro, the systemic exposures of metformin in vivo rats were not altered after metformin treatment with and without SB due to unchanged renal excretion of metformin...
November 7, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27812757/counter-flow-suggests-transport-of-dantrolene-and-5-oh-dantrolene-by-the-organic-anion-transporters-2-oat2-and-3-oat3
#9
Birgitta C Burckhardt, Maja Henjakovic, Yohannes Hagos, Gerhard Burckhardt
Dantrolene is the only available drug for the treatment of malignant hyperthermia, a life-threatening inborn sensitivity of the ryanodine receptor (RyR1) in skeletal muscles to volatile anesthetics. Dantrolene is metabolized in the liver to 5-OH dantrolene. Both compounds are zwitterions or net negatively charged. Here, we investigated interactions of dantrolene and 5-OH dantrolene with solute carrier (SLC) family members occurring in skeletal muscle cells, hepatocytes, and renal proximal tubule cells. SLC22A8 (organic anion transporter 3, OAT3) was very sensitive to both compounds exhibiting IC50 values of 0...
November 3, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27803672/autosomal-dominant-hypocalcemia-hypoparathyroidism-types-1-and-2
#10
REVIEW
Kelly L Roszko, Ruiye D Bi, Michael Mannstadt
Extracellular calcium is essential for life and its concentration in the blood is maintained within a narrow range. This is achieved by a feedback loop that receives input from the calcium-sensing receptor (CASR), expressed on the surface of parathyroid cells. In response to low ionized calcium, the parathyroids increase secretion of parathyroid hormone (PTH) which increases serum calcium. The CASR is also highly expressed in the kidneys, where it regulates the reabsorption of calcium from the primary filtrate...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27797596/pharmacokinetics-and-pharmacodynamics-of-sofosbuvir-and-ledipasvir-for-the-treatment-of-hepatitis-c
#11
Francisca Cuenca-Lopez, Antonio Rivero, Antonio Rivero-Juárez
The sofosbuvir (SOF) plus ledipasvir (LDV) fixed dose combination is the first direct action antiviral (DAA) single-treatment regimen (STR) to be commercialized. It is approved for the treatment of Hepatitis C virus (HCV) genotypes 1,3,4,5 and 6. Following approval in 2014, new pharmacokinetics and pharmacodynamics data were reported, which led to important clinical applications. Areas covered: This article reviews the pharmacokinetic and pharmacodynamic properties of the SOF/LDV fixed dose combination for the treatment of HCV...
October 31, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27795374/pharmacokinetic-pharmacodynamic-modeling-and-simulation-of-cefiderocol-a-parenteral-siderophore-cephalosporin-for-dose-adjustment-based-on-renal-function
#12
Takayuki Katsube, Toshihiro Wajima, Toru Ishibashi, Juan Camilo Arjona Ferreira, Roger Echols
The novel parenteral siderophore cephalosporin, cefiderocol, exhibits potent efficacy against most Gram-negative bacteria including carbapenem-resistant strains. Since cefiderocol is primarily excreted via the kidneys, this study was conducted to develop a population pharmacokinetic (PK) model to determine dose adjustment based on renal function.Population PK models were developed based on cefiderocol concentration data in plasma, urine and dialysate with a non-linear mixed effects model approach. Monte-Carlo simulations were conducted to calculate the probability of target attainment (PTA) of fraction of time during the dosing interval where the free drug concentration in plasma exceeds the minimum inhibitory concentration (MIC) (Tf>MIC) for a MIC range of 0...
October 17, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27785155/improper-hydration-induces-global-gene-expression-changes-associated-with-renal-development-in-infant-mice
#13
Chong-Su Kim, Dong-Mi Shin
BACKGROUND: The kidney is a major organ in which fluid balance and waste excretion is regulated. For the kidney to achieve maturity with functions, normal renal developmental processes need to occur. Comprehensive genetic programs underlying renal development during the prenatal period have been widely studied. However, postnatal renal development, from infancy to the juvenile period, has not been studied yet. Here, we investigated whether structural and functional kidney development was still ongoing in early life by analyzing the renal transcriptional networks of infant (4 weeks old) and juvenile (7 weeks old) mice...
2016: Genes & Nutrition
https://www.readbyqxmd.com/read/27780884/strength-of-evidence-for-labeled-dosing-recommendations-in-renal-impairment
#14
Joshua J Gagne, Nazleen F Khan, Tara S Raj, Lajja R Patel, Niteesh K Choudhry
BACKGROUND/AIMS: Renally excreted medications often require dose adjustment in patients with kidney impairment. While drug development and approval in the United States are typically based on several Phase I and II studies and one or more larger Phase III randomized trials, the basis for labeled dosing recommendations for patients with renal impairment is less well known. In response, we aimed to quantify the level of evidence used to recommend labeled dosing adjustments for newly approved drugs in patients with renal impairment...
October 24, 2016: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/27774431/diuretic-and-antiurolithiatic-activities-of-an-ethanolic-extract-of-acorus-calamus-l-rhizome-in-experimental-animal-models
#15
Hardik Ghelani, Maunik Chapala, Pinakin Jadav
Acorus calamus is a plant commonly used as a traditional herbal medicine and possesses the wide range of pharmacological applications. The present study investigated the diuretic and antiurolithiatic activities of an ethanolic extract of Acorus calamus L. (Family: Araceae) rhizome (EEAC). For diuretic activity, three doses of EEAC (250, 500 and 750 mg/kg) were studied, and measurement of the urinary volume and electrolytes (Na(+) and K(+)) concentration were taken as evaluation parameters. On the other hand, ethylene glycol induced urolithiasis (0...
October 2016: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/27760998/effective-uric-acid-lowering-treatment-for-hypertensive-patients-with-hyperuricemia
#16
Yuko Ohta, Azusa Ishizuka, Hisatomi Arima, Shinichiro Hayashi, Yoshio Iwashima, Masatsugu Kishida, Fumiki Yoshihara, Satoko Nakamura, Yuhei Kawano
Uric acid (UA) has been associated with hypertension, renal disease and cardiovascular disease. The aim of the present study was to compare the UA-lowering effects of a standard dose of the UA synthesis inhibitor febuxostat to a standard dose of the uricosuric agent benzbromarone, and to investigate the effects of a low-dose combination of both agents in hypertensive patients with hyperuricemia. Twenty hypertensive patients with inadequate UA control were administered febuxostat 40 mg (Feb), benzbromarone 50 mg (Ben) and febuxostat 20 mg and benzbromarone 25 mg (feb/ben) for 3 months each in a randomized modified crossover manner...
October 20, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/27756973/the-management-of-gout
#17
Andrew Finch Rheumatology, Paul Kubler Rheumatologist
Gout is a common inflammatory arthritis that is increasing in prevalence. It is caused by the deposition of urate crystals. Non-steroidal anti-inflammatory drugs, colchicine and corticosteroids are options for the management of acute gout. They are equally efficacious and comorbidities guide the best choice. Allopurinol is an effective treatment for reducing concentrations of uric acid. Renal function guides the starting dose of allopurinol and the baseline serum uric acid concentration guides the maintenance dose...
August 2016: Australian Prescriber
https://www.readbyqxmd.com/read/27754421/assessment-of-amino-acid-drug-transporters-for-renal-transport-of-18-f-fluciclovine-anti-18-f-facbc-in-vitro
#18
Masahiro Ono, Atsumi Baden, Hiroyuki Okudaira, Masato Kobayashi, Keiichi Kawai, Shuntaro Oka, Hirokatsu Yoshimura
[(18)F]Fluciclovine (trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid; anti-[(18)F]FACBC), a positron emission tomography tracer used for the diagnosis of recurrent prostate cancer, is transported via amino acid transporters (AATs) with high affinity (Km: 97-230 μM). However, the mechanism underlying urinary excretion is unknown. In this study, we investigated the involvement of AATs and drug transporters in renal [(18)F]fluciclovine reuptake. [(14)C]Fluciclovine (trans-1-amino-3-fluoro[1-(14)C]cyclobutanecarboxylic acid) was used because of its long half-life...
October 14, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27754002/js-ish-isn-1-oxidative-stress-the-kidney-and-hypertension-clinical-implications
#19
Christopher Wilcox
OBJECTIVE: CKD progression is accelerated by hypertension and impaired myogenic responses (MRs) of renal afferent arterioles leading to renal barotrauma. We tested the hypothesis that reactive oxygen species (ROS) underlie both these processes and that ROS metabolism by tempol would thereby protect kidneys. DESIGN AND METHODS: Rat and mouse 5/6 nephrectomy models of reduced renal mass (RRM) vs sham were fed high salt for 3 months during BP telemetry. Individual afferent arterioles were isolated and perfused...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753808/ssa-03-3-dietary-salt-intake-and-hypertension-in-singapore
#20
Vernon Min Sen Oh
According to the Singapore National Health Survey (NHS) of 2010, the population of the Republic of Singapore was 5.076,700, comprising four ethnic groups: Chinese (74.1%), Malays (13.4%), Indians (9.2%), and others (3.3%). The National Health Survey for 2016 is under way and due to be published in 2017. From the six-yearly national health surveys, the crude prevalence of clinical hypertension (HTn), defined as a sustained blood pressure ≥ 140/90 mmHg, in Singaporean residents aged 30 to 69 years rose from 22...
September 2016: Journal of Hypertension
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