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Renal excretion of drugs

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https://www.readbyqxmd.com/read/29744119/levetiracetam-induced-transaminitis-in-a-young-male-with-traumatic-brain-injury
#1
Vivekananda Rachamallu, Michael M Song, Jace M Reed, Manish Aligeti
Levetiracetam is a commonly prescribed antiepileptic drug for seizure prophylaxis in patients with traumatic brain injury (TBI). Levetiracetam metabolism has been reported to be non-dependent on hepatic cytochrome P450 (CYP450) isoenzyme system. Furthermore, levetiracetam and its metabolites are reported to be eliminated from systemic circulation via renal excretion. Therefore, due to its well-known renal clearance mechanism with no dosage adjustments recommended for hepatic impairment, levetiracetam is often chosen as the drug of choice in patients with suspected or ongoing hepatic dysfunction...
November 2017: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/29742345/tumor-specific-and-renal-excretable-star-like-tri-block-polymer-doxorubicin-conjugates-for-safe-and-efficient-anticancer-therapy
#2
Hao Tang, Jiajing Zhang, Jin Tang, Yi Shen, Wenxuan Guo, Min Zhou, Ruihua Wang, Ni Jiang, Zhihua Gan, Qingsong Yu
Efficient tumor accumulation and body clearance are two paralleled requirement for ideal nanomedicines. However, it's hard for both to be met simultaneously. The inefficient clearance often restrains the application of drug delivery systems (DDSs), especially for high-dosage administration. In this study, the star-like and block structures are combined to enhance the tumor specific targeting of the parent structures and obtain additional renal excretion property. The influences of polymer architectures and chemical compositions on the physicochemical and biological properties, particularly the simultaneous achievement of tumor accumulation and renal clearance have been investigated...
May 9, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29736201/niclosamide-ethanolamine-improves-diabetes-and-diabetic-kidney-disease-in-mice
#3
Pengxun Han, Mumin Shao, Lan Guo, Wenjing Wang, Gaofeng Song, Xuewen Yu, Chunlei Zhang, Na Ge, Tiegang Yi, Shunmin Li, Heng Du, Huili Sun
Diabetes and its renal complications are major medical challenges worldwide. There are no effective drugs currently available for treating diabetes and diabetic kidney disease (DKD), especially in type 1 diabetes (T1D). Evidence has suggested that niclosamide ethanolamine salt (NEN) could improve diabetic symptoms in mice of type 2 diabetes (T2D). However, its role in T1D and DKD has not been studied to date. Here we report that NEN could protect against diabetes in streptozotocin (STZ) induced T1D mice. It increased serum insulin levels, corrected the unbalanced ratio of α-cells to β-cells, and induced islet morphologic changes under diabetic conditions...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29720497/molecular-mechanisms-for-species-differences-in-organic-anion-transporter-1-oat1-implications-for-renal-drug-toxicity
#4
Ling Zou, Adrian Stecula, Anshul Gupta, Bhagwat Prasad, Huan-Chieh Chien, Sook Wah Yee, Li Wang, Jashvant D Unadkat, Simone H Stahl, Katherine S Fenner, Kathleen M Giacomini
Species differences in renal drug transporters continue to plague drug development with animal models failing to adequately predict renal drug toxicity. For example, adefovir, a renally excreted antiviral drug, failed clinical studies for HIV due to pronounced nephrontoxicity in humans. In this study, we demonstrated that there are large species differences in the kinetics of interactions of a key class of antiviral drugs, acyclic nucleoside phosphonates (ANPs), with OAT1 (SLC22A6) and identified a key amino acid residue responsible for these differences...
May 2, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29701197/-role-of-drug-transporters-in-rational-use-of-drugs-at-high-altitude-area
#5
Wenbin Li, Baohua Yan, Rong Wang, Zhengping Jia
Pharmacokinetics plays a key role in rational use of medicines. Many factors can affect the drug's pharmacokinetics. Previous studies mainly focused on the impact of hypoxia on hepatic drug metabolizing enzyme, but uncommon on drug transporters. Actually, drug transporter is a key factor for activation of the drugs transport across the cell membrane into the inside of cells, such as multidrug resistance protein (MDR), breast cancer resistance protein (BCRP), multidrug resistance associated protein (MRP), organic cation transporter (OCT), organic anion-transporting polypeptide (OATP), organic anion transporter (OAT), qligopeptide transporter (PEPT), etc...
March 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29695165/pharmacokinetics-pharmacodynamics-of-dabigatran-75-mg-twice-daily-in-patients-with-nonvalvular-atrial-fibrillation-and-severely-impaired-renal-function
#6
Jack L Martin, Habib Esmaeili, Raymond C Manuel, Michaela Petrini, Sabrina Wiebe, Hugo Maas
INTRODUCTION: Dabigatran etexilate is an oral direct thrombin inhibitor. Dabigatran excretion is 80% renal, so exposure increases with severity of renal failure. The US Food and Drug Administration-approved dabigatran etexilate 75 mg twice daily (BID) for patients with nonvalvular atrial fibrillation (NVAF) having severely impaired renal function (creatinine clearance: 15-30 mL/min), based on post hoc pharmacokinetic modeling. We assessed dabigatran exposure at trough and peak levels in patients with NVAF and severely impaired renal function and compared with model predictions...
January 1, 2018: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29688628/pharmacokinetics-pharmacodynamics-and-tolerability-of-concomitant-administration-of-verinurad-and-febuxostat-in-healthy-male-volunteers
#7
Jesse Hall, Michael Gillen, Xiaojuan Yang, Zancong Shen
Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in development for treatment of gout and asymptomatic hyperuricemia. This phase 1, single-blind, multiple-dose, drug-drug interaction study evaluated the pharmacokinetics (PK), pharmacodynamics, and safety/tolerability of verinurad in combination with febuxostat in healthy male volunteers. Twenty-three subjects were randomized and received once-daily doses of verinurad (or placebo) or febuxostat alone (days 1-7 and days 15-21), or verinurad + febuxostat on days 8-14...
April 24, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29663413/predicting-pharmacokinetics-pharmacodynamics-in-the-individual-patient-separating-reality-from-hype
#8
REVIEW
Leslie Z Benet
Individualization of patient drug dosing to maximize efficacy and minimize toxicity is the goal of clinical pharmacology. Here we review the history of drug dosing individualization from early predictions for renally eliminated drugs based on kidney function through the introduction of clearance concepts for metabolic processes, the differentiation of volume of distribution between pharmacokinetics and chemistry, the role of transporters, the unique pharmacokinetic aspects of oral dosing, and the relevance of protein binding to the emergence of pharmacogenomics...
April 17, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29658375/pharmacokinetic-alterations-in-poloxamer-407-induced-hyperlipidemic-rats
#9
Unji Lee, Mi Hye Kwon, Hee Eun Kang
1. Plasma lipid profile abnormalities in hyperlipidemia can potentially alter the pharmacokinetics of a drug in a complex manner. To evaluate these pharmacokinetic alterations in hyperlipidemia and to determine the underlying mechanism(s), poloxamer 407-induced hyperlipidemic rats (HL rats), a well-established animal model of hyperlipidemia have been used. 2. In this review, we summarize findings on the pathophysiological and gene expression changes in drug-metabolizing enzymes and transporters in HL rats. We discuss pharmacokinetic changes in drugs metabolized primarily via hepatic cytochrome P450 (CYPs) in terms of alterations in hepatic intrinsic clearance (CL'int ), free fraction in plasma (fu ), and hepatic blood flow rate (QH ), depending on the hepatic excretion ratio, as well as drugs eliminated primarily by mechanisms other than hepatic CYPs...
April 16, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29657939/cisplatin-alters-sodium-excretion-and-renal-clearance-in-rats-gender-and-drug-dose-related
#10
Sima Jilanchi, Ardeshir Talebi, Mehdi Nematbakhsh
Background: Nephrotoxicity is one of the side effects of cisplatin (CP) therapy which is gender related. CP disturbs renal function through glomerular filtration rate and electrolytes transport disturbances. This study was designed to compare some markers related to renal function in two protocols of CP treatment in rats. Materials and Methods: Male and female rats were subjected to receive single (treat 1; 7.5 mg/kg) and continues doses (treat 2; 3 mg/kg/day for 5 days) of CP, and the measurements were compared with control animals...
2018: Advanced Biomedical Research
https://www.readbyqxmd.com/read/29589183/new-diabetes-therapies-and-diabetic-kidney-disease-progression-the-role-of-sglt-2-inhibitors
#11
REVIEW
Claire C J Dekkers, Ron T Gansevoort, Hiddo J L Heerspink
PURPOSE OF REVIEW: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors have emerged as a promising drug class for the treatment of diabetic kidney disease. Developed originally as glucose-lowering drugs by enhancing urinary glucose excretion, these drugs also lower many other renal and cardiovascular risk factors such as body weight, blood pressure, albuminuria, and uric acid. Results from the EMPA-REG OUTCOME and CANVAS trials show that these salutary effects translate into a reduction in cardiovascular outcomes and have the potential to delay the progression of kidney function decline...
March 27, 2018: Current Diabetes Reports
https://www.readbyqxmd.com/read/29588531/review-of-case-reports-on-hyperkalemia-induced-by-dietary-intake-not-restricted-to-chronic-kidney-disease-patients
#12
REVIEW
Rogier P M Te Dorsthorst, Jytte Hendrikse, Mats T Vervoorn, Valerie Y H van Weperen, Marcel A G van der Heyden
Hyperkalemia is a metabolic disturbance of the potassium balance that can cause potentially fatal cardiac arrhythmias. Kidney dysfunction and renin-angiotensin-aldosterone system inhibiting drugs are notorious for their tendency to induce hyperkalemia by decreasing the excretion of potassium. The role of dietary potassium intake in inducing hyperkalemia is less clear. We review and analyze the common presentation, laboratory, and electrocardiogram (ECG) findings and therapeutic options associated with dietary-induced hyperkalemia, and find evidence for hyperkalemia development in non-renal impaired patients...
March 27, 2018: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/29578360/efficacy-and-safety-of-interleukin-1-inhibitors-in-familial-mediterranean-fever-patients-complicated-with-amyloidosis
#13
Özkan Varan, Hamit Kucuk, Hakan Babaoglu, Serdar Can Guven, Mehmet Akif Ozturk, Seminur Haznedaroglu, Berna Goker, Abdurrahman Tufan
Absract Background: Colchicine is the mainstay of the treatment of familial Mediterranean fever (FMF). However, 10% of FMF patients do not respond well to colchicine. Efficacy of IL-1 inhibitors in reducing attacks have been demonstrated in colchicine resistant FMF (crFMF) patients recently. Colchicine is still the only approved drug for the prevention of amyloidosis in FMF and utility of IL-1 inhibitors in crFMF cases who already has amyloidosis remain to be elucidated. Herein, we evaluated efficacy and safety of IL-1 inhibitors in patients with crFMF-associated AA amyloidosis in a relatively large single center study...
March 26, 2018: Modern Rheumatology
https://www.readbyqxmd.com/read/29565959/identifying-levorphanol-ingestion-using-urine-biomarkers-in-health-care-patients
#14
Amber R Watson, Ali Roberts
BACKGROUND: Levorphanol is a long-acting opioid analgesic that is an optical isomer of dextrorphan, a metabolite of the over-the-counter cough suppressant dextromethorphan. Providers prescribing levorphanol for pain management may need to assess compliance through urine drug testing, as this agent is subject to abuse. Therefore, it is important to differentiate between dextromethorphan and levorphanol ingestion. OBJECTIVES: This article is the first to report urine concentrations of levorphanol/dextrorphan and 3-hydroxymorphinan in human urine and assesses the need for an enantiomeric analysis to distinguish between dextromethorphan and levorphanol ingestion...
March 2018: Pain Physician
https://www.readbyqxmd.com/read/29562664/aptamer-therapeutics-in-cancer-current-and-future
#15
REVIEW
Yoshihiro Morita, Macall Leslie, Hiroyasu Kameyama, David E Volk, Takemi Tanaka
Aptamer-related technologies represent a revolutionary advancement in the capacity to rapidly develop new classes of targeting ligands. Structurally distinct RNA and DNA oligonucleotides, aptamers mimic small, protein-binding molecules and exhibit high binding affinity and selectivity. Although their molecular weight is relatively small-approximately one-tenth that of monoclonal antibodies-their complex tertiary folded structures create sufficient recognition surface area for tight interaction with target molecules...
March 19, 2018: Cancers
https://www.readbyqxmd.com/read/29561839/ccr2-antagonism-leads-to-marked-reduction-in-proteinuria-and-glomerular-injury-in-murine-models-of-focal-segmental-glomerulosclerosis-fsgs
#16
Zhenhua Miao, Linda S Ertl, Dale Newland, Bin Zhao, Yu Wang, Xiaoping Zang, James J Campbell, Xiaoli Liu, Ton Dang, Shichang Miao, Antoni Krasinski, Sreenivas Punna, Yibin Zeng, Jeffrey McMahon, Penglie Zhang, Israel F Charo, Thomas J Schall, Rajinder Singh
Focal segmental glomerulosclerosis (FSGS) comprises a group of uncommon disorders that present with marked proteinuria, nephrotic syndrome, progressive renal failure and characteristic glomerular lesions on histopathology. The current standard of care for patients with FSGS include immunosuppressive drugs such as glucocorticoids followed by calcineurin inhibitors, if needed for intolerance or inadequate response to glucocorticoids. Renin-angiotensin-aldosterone (RAAS) blockers are also used to control proteinuria, an important signature of FSGS...
2018: PloS One
https://www.readbyqxmd.com/read/29557529/clinical-pharmacokinetics-and-drug-drug-interactions-of-elbasvir-grazoprevir
#17
Tony K L Kiang
Elbasvir and grazoprevir, in a fixed-dose combination of 50 and 100 mg, respectively, have received approval to be administered orally once daily, with or without ribavirin, for the treatment of chronic hepatitis C virus (HCV) infections. The absorption characteristics of elbasvir and grazoprevir have been adequately summarized, although differences were observed for grazoprevir (e.g., increased exposure at steady state in patients), but not elbasvir, between healthy and HCV-infected subjects. Inconsistencies with respect to absorption were also reported on the effects of food or acid reducers (famotidine or pantoprazole) in the literature...
March 20, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29534286/clinical-pharmacokinetics-and-pharmacodynamics-of-etelcalcetide-a-novel-calcimimetic-for-treatment-of-secondary-hyperparathyroidism-in-patients-with-chronic-kidney-disease-on-hemodialysis
#18
REVIEW
Benjamin Wu, Murad Melhem, Raju Subramanian, Ping Chen, Bethlyn Jaramilla Sloey, Bruno Fouqueray, M Benjamin Hock, Gary L Skiles, Andrew T Chow, Edward Lee
Etelcalcetide, a d-amino acid peptide, is an intravenous calcimimetic approved for the treatment of secondary hyperparathyroidism. Etelcalcetide binds the calcium-sensing receptor and increases its sensitivity to extracellular calcium, thereby decreasing secretion of parathyroid hormone (PTH) by chief cells. Etelcalcetide and its low-molecular-weight transformation products are rapidly cleared by renal excretion in healthy subjects, but clearance is substantially reduced and dependent on hemodialysis in end-stage renal disease...
March 13, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29532519/contrasting-effects-on-the-risk-of-macrovascular-and-microvascular-events-of-antihyperglycemic-drugs-that-enhance-sodium-excretion-and-lower-blood-pressure
#19
REVIEW
M Packer
Three classes of anti-hyperglycaemic medications are distinguished by their urinary sodium excretion-enhancing and blood pressure-lowering actions: long-acting glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors. Yet, these drugs exert different effects on macrovascular risk. Glucagon-like peptide-1 receptor agonists reduce atherosclerotic thromboembolic events, but have little effect on heart failure; sodium-glucose co-transporter-2 inhibitors decrease the occurrence of heart failure, but have minimal effect on myocardial infarction and stroke; and dipeptidyl peptidase-4 inhibitors do not ameliorate either atherosclerotic thromboembolic events or heart failure...
June 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29525332/worsening-heart-failure-during-the-use-of-dpp-4-inhibitors-pathophysiological-mechanisms-clinical-risks-and-potential-influence-of-concomitant-antidiabetic-medications
#20
REVIEW
Milton Packer
Although dipeptidyl peptidase (DPP)-4 inhibitors have been reported to have a neutral effect on thromboembolic vaso-occlusive events in large-scale trials, they act to potentiate several endogenous peptides that can exert deleterious cardiovascular effects. Experimentally, DPP-4 inhibitors may augment the ability of glucagon-like peptide-1 to stimulate cyclic adenosine monophosphate in cardiomyocytes, and potentiation of the effects of stromal cell-derived factor-1 by DPP-4 inhibitors may aggravate cardiac fibrosis...
March 1, 2018: JACC. Heart Failure
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