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https://www.readbyqxmd.com/read/29341179/better-characterization-of-vinflunine-pharmacokinetics-variability-and-exposure-toxicity-relationship-to-improve-its-use-analyses-from-18-trials
#1
A Schmitt, L Nguyen, G Zorza, P Ferré, A Pétain
AIMS: Vinflunine is a novel tubulin-targeted inhibitor indicated as a single agent for the treatment of bladder cancers after failure of prior platinum-based therapy. Its pharmacokinetics (PK) and pharmacodynamics (PD) have been independently characterized through several phase I and phase II studies. However, no global pharmacometric analysis had been conducted yet. METHODS: Vinflunine concentrations and safety data from 18 phase I and phase II studies were used to conduct population PK and PK/PD analysis, using Nonmem...
January 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29341028/ameliorative-effects-of-zataria-multiflora-hydro-alcoholic-extract-on-gentamicin-induced-nephrotoxicity-in-rats
#2
Saeed Hajihashemi, Tahereh Jafarian, Mahboubeh Ahmadi, Ali Rahbari, Fatemeh Ghanbari
BACKGROUND: Nephrotoxicity is the major side effects of aminoglycoside antibiotics such as gentamicin. The aim of this study was to investigate the therapeutic effects of Z.multiflora (ZM) hydroalcoholic extract on gentamicin-induced nephrotoxicity. METHODS: Twenty-eight male Wistar rats categorized into four groups: 1) the control group without injection, 2) the gentamicin treated group (100 mg/kg, i.p) 3) the gentamicin and Z. Multiflora treated group; Z. Multiflora extract(0...
January 16, 2018: Drug Research
https://www.readbyqxmd.com/read/29338932/functional-characteristics-of-a-renal-h-lipophilic-cation-antiport-system-in-porcine-llc-pk1-cells-and-rats
#3
Ryutaro Matsui, Ryutaro Hattori, Youhei Usami, Masumi Koyama, Yuki Hirayama, Emi Matsuba, Yukiya Hashimoto
We have recently found an H+/quinidine (a lipophilic cation, QND) antiport system in Madin-Darby canine kidney (MDCK) cells. The primary aim of the present study was to evaluate whether the H+/lipophilic cation antiport system is expressed in porcine LLC-PK1 cells. That is, we investigated uptake and/or efflux of QND and another cation, bisoprolol, in LLC-PK1 cells. In addition, we studied the renal clearance of bisoprolol in rats. Uptake of QND into LLC-PK1 cells was decreased by acidification of the extracellular pH or alkalization of the intracellular pH...
December 5, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29335891/serum-bilirubin-concentration-is-associated-with-left-ventricular-remodeling-in-patients-with-type-2-diabetes-mellitus-a-cohort-study
#4
Tomoaki Inoue, Noriyuki Sonoda, Shinsuke Hiramatsu, Shinichiro Kimura, Yoshihiro Ogawa, Toyoshi Inoguchi
INTRODUCTION: Previous studies have shown that serum bilirubin concentration is inversely associated with the risk of cardiovascular disease. The relationship between serum bilirubin concentration and left ventricular geometry, however, has not been investigated in patients with diabetes mellitus. METHODS: In this cohort study, 158 asymptomatic patients with type 2 diabetes mellitus without overt heart disease were enrolled. Left ventricular structure and function were assessed using echocardiography...
January 15, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29331868/zinc-supplementation-alleviates-the-progression-of-diabetic-nephropathy-by-inhibiting-the-overexpression-of-oxidative-stress-mediated-molecular-markers-in-streptozotocin-induced-experimental-rats
#5
Susmita Barman, Seetur R Pradeep, Krishnapura Srinivasan
Zinc deficiency during diabetes projects a role for zinc nutrition in the management of diabetic nephropathy. The current study explored whether zinc supplementation protects against diabetic nephropathy through modulation of kidney oxidative stress and stress-induced expression related to the inflammatory process in streptozotocin-induced diabetic rats. Groups of hyperglycemic rats were exposed to dietary interventions for 6 weeks with zinc supplementation (5 times and 10 times the normal level). Supplemental-zinc-fed diabetic groups showed a significant reversal of increased kidney weight and creatinine clearance...
December 11, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29331653/gallic-acid-attenuates-type-i-diabetic-nephropathy-in-rats
#6
Mayuresh Sudamrao Garud, Yogesh Anant Kulkarni
Literatures suggest that TGF-β1 have a central role in the progression of diabetic nephropathy and its down regulation can improve the disease condition. Oxidative stress, generation of advanced glycation end products and activation of renin angiotensin system are the connecting links between hyperglycemia and TGF-β1 over expression. Gallic acid is a phytochemical having wide range of biological activities. Gallic acid is reported to have antioxidant and advanced glycation inhibitory activity. It has also shown inhibitory effects on angiotensin converting enzyme...
January 10, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29331383/population-pharmacokinetics-of-high-dose-methotrexate-in-patients-with-primary-central-nervous-system-lymphoma
#7
Shenghui Mei, Xingang Li, Xueyun Jiang, Kefu Yu, Song Lin, Zhigang Zhao
The intra- and inter-individual variances of methotrexate (MTX) pharmacokinetics are extremely large, and the pharmacokinetic property of MTX in patients with primary central nervous system lymphoma (PCNSL) is unestablished. A total of 701 MTX plasma concentrations from 98 patients with PCNSL under High-dose methotrexate (HDMTX) therapy were used to develop the population pharmacokinetic (popPK) model of MTX by using the nonlinear mixed-effects modeling method. A two-compartment model was employed to describe the pharmacokinetic property of MTX...
January 10, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29329957/safety-and-tolerability-of-a-novel-polyclonal-human-anti-mers-coronavirus-antibody-produced-from-transchromosomic-cattle-a-phase-1-randomised-double-blind-single-dose-escalation-study
#8
John H Beigel, Jocelyn Voell, Parag Kumar, Kanakatte Raviprakash, Hua Wu, Jin-An Jiao, Eddie Sullivan, Thomas Luke, Richard T Davey
BACKGROUND: Middle East respiratory syndrome (MERS) is a severe respiratory illness with an overall mortality of 35%. There is no licensed or proven treatment. Passive immunotherapy approaches are being developed to prevent and treat several human medical conditions where alternative therapeutic options are absent. We report the safety of a fully human polyclonal IgG antibody (SAB-301) produced from the hyperimmune plasma of transchromosomic cattle immunised with a MERS coronavirus vaccine...
January 9, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29329489/mycophenolic-acid-and-its-metabolites-in-kidney-transplant-recipients-a-semimechanistic-enterohepatic-circulation-model-to-improve-estimating-exposure
#9
Malek Okour, Pamala A Jacobson, Mariam A Ahmed, Ajay K Israni, Richard C Brundage
Mycophenolic acid (MPA) is an approved immunosuppressive agent widely prescribed to prevent rejection after kidney transplantation. Wide between-subject variability (BSV) in MPA exposure exists which in part may be due to variability in enterohepatic recirculation (EHC). Several modeling strategies were developed to evaluate EHC as part of MPA pharmacokinetics, however mechanistic representation of EHC is limited. These models have not provided a satisfactory representation of the physiology of EHC in their modeling assumptions...
January 12, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29325686/phase-ii-study-of-tailored-s-1-monotherapy-with-a-1-week-interval-after-a-2-week-dosing-period-in-elderly-patients-with-advanced-non-small-cell-lung-cancer
#10
Hisatsugu Goto, Yoshio Okano, Hisanori Machida, Nobuo Hatakeyama, Fumitaka Ogushi, Takashi Haku, Takanori Kanematsu, Tomoyuki Urata, Soji Kakiuchi, Masaki Hanibuchi, Saburo Sone, Yasuhiko Nishioka
BACKGROUND: S-1 is an oral fluoropyrimidine that is active in the treatment of non-small cell lung cancer (NSCLC); however, an optimal treatment schedule and appropriate dose adjustments of S-1 in elderly patients have not yet been established. METHODS: We conducted a phase II trial to evaluate the efficacy and safety of a 2-week S-1 monotherapy treatment followed by a 1-week interval as a first-line treatment of elderly NSCLC patients, by adjusting the dose based on the individual creatinine clearance (Ccr) and body surface area (BSA)...
January 2018: Respiratory Investigation
https://www.readbyqxmd.com/read/29324683/pentoxifylline-and-methylprednisolone-additively-alleviate-kidney-failure-and-prolong-survival-of-rats-after-renal-warm-ischemia-reperfusion
#11
Grzegorz Wystrychowski, Wojciech Wystrychowski, Władysław Grzeszczak, Andrzej Więcek, Robert Król, Antoni Wystrychowski
Renal ischemia-reperfusion injury (IRI) induces local inflammation leading to kidney damage. Since pentoxifylline (PTX) and steroids have distinct immunomodulatory properties, we aimed to evaluate for the first time their combined use in IRI-induced acute kidney injury (AKI) and chronic kidney disease (CKD) in rats. In two experiments, PTX (100 mg/kg body weight subcutaneously) was administered 90 min prior to renal IRI or/and methylprednisolone (MP; 100 mg/kg body weight intramuscularly) was infused 60 min after reperfusion of a solitary kidney (AKI model: 45 min ischemia, 48 male Sprague-Dawley rats) or one kidney with excision of contralateral kidney 2 weeks later (CKD model: 90 min ischemia, 38 rats)...
January 11, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29322215/-assessment-of-kidney-function-creatinine-is-not-the-whole-story
#12
REVIEW
U Huynh-Do, M Fiedler, B Vogt
Chronic renal insufficiency has a high prevalence and leads not only to a severe impairment in the quality of life but also to a higher mortality, mainly due to cardiovascular complications; however, in the early stages where there is still a chance for a therapeutic intervention, it is often underestimated because depending on endogenous factors (e.g. age and muscle mass), serum creatinine could falsely remain in the normal range while kidney function is already impaired. An exact measurement of the glomerular filtration rate (GFR) using radionuclide techniques is cumbersome and usually confined to rare cases, such as in clinical studies...
January 10, 2018: Der Internist
https://www.readbyqxmd.com/read/29319495/investigation-of-the-age-dependency-of-vancomycin-clearance-by-population-pharmacokinetic-modeling
#13
Muhammad Usman, Manfred Fobker, Georg Hempel
PURPOSE: The aim of this study was to evaluate the influence of age and other possible covariates on vancomycin clearance in order to define a possible cut off value of age for dose optimization in elderly patients from data obtained during therapeutic drug monitoring. MATERIALS AND METHODS: Population pharmacokinetic analysis of 256 samples obtained from 144 patients was performed by using NONMEM®. A one-compartment model was applied as the base model with first-order conditional estimation method with interaction (FOCE-I)...
January 10, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29316960/pregabalin-versus-gabapentin-in-the-treatment-of-sciatica-study-protocol-for-a-randomised-double-blind-cross-over-trial-pagpros
#14
Kelvin Robertson, Laurence A G Marshman, Maria Hennessy, Linton Harriss, David Plummer
BACKGROUND: There is currently an absence of high-grade evidence regarding the treatment of chronic sciatica (CS). Whilst gabapentin (GBP) and pregabalin (PGB) are both currently used to treat CS, equipoise exists regarding their individual use. In particular, no head-to-head study of GBP and PGB in CS exists. Despite equipoise, most countries' formulary regulatory authorities typically favour one drug for subsidy over the other. This hinders interchange wherever the favoured drug is either ineffective or not tolerated...
January 9, 2018: Trials
https://www.readbyqxmd.com/read/29316531/graphene-oxide-doping-improves-the-biocompatibility-and-separation-performance-of-polyethersulfone-hollow-fiber-membranes-for-bioartificial-kidney-application
#15
Akshay Modi, Surendra Kumar Verma, Jayesh Bellare
HYPOTHESIS: Graphene oxide (GO)-doping in polyethersulfone hollow fiber membranes (PES HFMs) improves the biocompatibility and separation performance for bioartificial kidney (BAK) application. EXPERIMENTS: GO was doped in PES HFMs. The physicochemical characterization of the developed HFMs was carried out. The biocompatibility tests including hemocompatibility and cytotoxicity tests, and separation experiments including uremic toxins clearance were performed. FINDINGS: GO-doping resulted in low hemolysis (0...
December 27, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/29315736/dosing-oxaliplatin-in-a-haemodialysis-patient-with-metastatic-rectum-cancer-monitored-by-free-platinum-concentrations
#16
I R F van Berlo-van de Laar, W J Brummelhuis, A L T Imholz, J H Schellens, A D R Huitema, F G A Jansman
WHAT IS KNOWN AND OBJECTIVE: Oxaliplatin in combination with fluorouracil and folinic acid is one of the preferred chemotherapeutic options in the treatment of metastatic rectum cancer. However, oxaliplatin is contraindicated in patients with a creatinine clearance <30 mL/min and dosing guidelines in patients on haemodialysis have not been established. CASE SUMMARY: A 77-year-old haemodialysis patient with metastatic rectum cancer was treated with FOLFOX and bevacizumab (oxaliplatin 70 mg/m2 , folinic acid 200 mg/m2 , 5-FU 340 mg/m2 bolus and 2040 mg/m2 continuous infusion during 44 hours and bevacizumab 5 mg/kg) every three weeks...
January 5, 2018: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29315212/higher-protein-intake-is-not-associated-with-decreased-kidney-function-in-pre-diabetic-older-adults-following-a-one-year-intervention-a-preview-sub-study
#17
Grith Møller, Jens Rikardt Andersen, Christian Ritz, Marta P Silvestre, Santiago Navas-Carretero, Elli Jalo, Pia Christensen, Elizabeth Simpson, Moira Taylor, J Alfredo Martinez, Ian Macdonald, Nils Swindell, Kelly A Mackintosh, Gareth Stratton, Mikael Fogelholm, Thomas M Larsen, Sally D Poppitt, Lars O Dragsted, Anne Raben
Concerns about detrimental renal effects of a high-protein intake have been raised due to an induced glomerular hyperfiltration, since this may accelerate the progression of kidney disease. The aim of this sub-study was to assess the effect of a higher intake of protein on kidney function in pre-diabetic men and women, aged 55 years and older. Analyses were based on baseline and one-year data in a sub-group of 310 participants included in the PREVIEW project (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World)...
January 9, 2018: Nutrients
https://www.readbyqxmd.com/read/29314721/peritoneal-protein-losses-depend-on-more-than-just-peritoneal-dialysis-modality-and-peritoneal-membrane-transporter-status
#18
Suree Yoowannakul, Lauren S Harris, Andrew Davenport
Peritoneal protein clearance (PPCl) depends upon vascular supply and size selective permeability. Some previous reports suggested PPCl can distinguish fast peritoneal membrane transport due to local or systemic inflammation. However, as studies have been discordant, we wished to determine factors associated with an increased PPCl. Consecutive patients starting peritoneal dialysis (PD) who were peritonitis-free were studied. Data included a baseline peritoneal equilibration test (PET), measurement of dialysis adequacy, 24-h dialysate PPCl and body composition measured by multifrequency bioimpedance...
January 4, 2018: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/29311069/meropenem-vaborbactam-single-dose-pharmacokinetics-and-safety-in-subjects-with-chronic-renal-impairment
#19
Christopher M Rubino, Sujata M Bhavnani, Jeffery S Loutit, Brooke Lohse, Michael N Dudley, David C Griffith
Vaborbactam is a member of a new class of β-lactamase inhibitors with inhibitory activity against serine carbapenemases (e.g. Klebsiella pneumoniae carbapenemase) that has been developed in combination with meropenem. Pharmacokinetics of the combination were evaluated in 41 subjects with chronic renal impairment in a Phase 1, open-label, single-dose study. Subjects were assigned to one of five groups based on renal function: normal (creatinine clearance ≥90 mL/min), mild (estimated glomerular filtration rate [eGFR] 60-89 mL/min/1...
January 8, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29310327/prevalence-and-clinical-characteristics-of-pseudohypertension-in-elderly-patients-prepared-for-coronary-artery-angiography
#20
Xixi Dai, Haiya Wang, Ningyuan Fang
BACKGROUND: Pseudohypertension (PHT) can cause adverse effects in the elderly owing to administration of antihypertension therapy. The present study aimed to determine the prevalence of PHT in the elderly and associated risk factors to investigate a noninvasive method of detection of PHT. METHODS: We recruited 151 patients (age ≥60 years) who underwent coronary angiography. Demographic and clinical data were collected from the patients. During coronary angiography, intrabrachial arterial pressure and indirect blood pressure were measured...
December 2017: Medicine (Baltimore)
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