journal
MENU ▼
Read by QxMD icon Read
search

Clinical and Translational Science

journal
https://www.readbyqxmd.com/read/28088839/pharmacokinetic-pharmacodynamic-modeling-of-the-pde4-inhibitor-tak-648-in-type-2-diabetes-early-translational-approaches-for-human-dose-prediction
#1
N Plock, S Vollert, M Mayer, G Hanauer, G Lahu
TAK-648 is a PDE4 inhibitor with demonstrated preclinical antidiabetic properties. Our objective was to develop a translational pharmacokinetic/pharmacodynamic (PK/PD) model for human type 2 diabetes (T2D) dose prediction using HbA1c results from a db/db mouse study. Estimated parameters in combination with tPDE4i values calculated for the clinical roflumilast dose of 500 μg were used to translate preclinical effects of TAK-648 to required exposure in humans. A first-in-human study with single TAK-648 doses of 0...
January 15, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28083989/final-nih-policy-on-the-use-of-a-single-institutional-review-board-for-multi-site-research
#2
Valery M Gordon, Michelle A Culp, Carrie D Wolinetz
For nearly 50 years, the Common Rule has required Institutional Review Board (IRB) oversight of federally-funded research to protect the rights and welfare of human research participants. Over time, research has changed and research studies often involve multiple sites. Recognizing that research policies must evolve with science and ensure both efficiency and protections for research participants, NIH released a Policy on the Use of a Single Institutional Review Board for Multi-Site Research in June 2016. This article is protected by copyright...
January 13, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28083940/personalised-medicine-in-europe
#3
Elmar Nimmesgern, Indridi Benediktsson, Irene Norstedt
Personalised medicine is a promising new concept for dealing with challenges of health and health systems. With the launch of the International Consortium of Personalised Medicine, which brings together health research funders and policy making organisations, European countries aim to coordinate research and health policy to advance the implementation of personalised medicine. This article is protected by copyright. All rights reserved.
January 12, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28079301/case-study-for-lean-management-in-the-public-sector-improving-combination-product-review-at-the-food-drug-administration
#4
Michael J Rappel, Nina L Hunter, April I Alexandrow, Kyle O Hair, Rachel E Sherman, Robert M Califf
Therapeutics known as combination products because they combine drug, device, and/or biologic elements can offer important advantages relative to single-modality products. However, regulatory policy in this arena has lagged relative to increases in product submissions and complexity of these products. In this article, we describe how the US Food and Drug Administration (FDA) applied Lean management methods to improve and streamline the process by which different FDA Centers and Offices coordinate review of combination products...
January 12, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28078768/microphysiological-systems-organs-on-chips-for-drug-efficacy-and-toxicity-testing
#5
Lucie A Low, Danilo A Tagle
No abstract text is available yet for this article.
January 11, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28075528/prospective-evaluation-of-genetic-variation-in-platelet-endothelial-aggregation-receptor-1-reveals-aspirin-dependent-effects-on-platelet-aggregation-pathways
#6
J D Backman, L M Yerges-Armstrong, R B Horenstein, S Newcomer, S Shaub, M Morrisey, P Donnelly, M Drolet, K Tanner, M A Pavlovich, J R O'Connell, B D Mitchell, J P Lewis
Genetic variation in the platelet endothelial aggregation receptor 1 (PEAR1) gene, most notably rs12041331, is implicated in altered on-aspirin platelet aggregation and increased cardiovascular event risk. We prospectively tested the effects of aspirin administration at commonly prescribed doses (81, 162, and 324 mg/day) on agonist-induced platelet aggregation by rs12041331 genotype in 67 healthy individuals. Prior to aspirin administration, rs12041331 minor allele carriers had significantly reduced adenosine diphosphate (ADP)-induced platelet aggregation compared with noncarriers (P = 0...
January 11, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/27996196/reverse-translational-study-of-fenofibrate-s-observed-effects-in-diabetes-associated-retinopathy
#7
R A Farris, E T Price
Clinical trials suggest that fenofibrate reduces the progression of retinopathies in patients with type 2 diabetes. Furthermore, patients with retinopathies have elevated levels of inflammatory chemokines and dysfunctional retinal angiogenesis. Therefore, we investigated the effects of fenofibrate on the production of inflammatory chemokines and genes associated with angiogenesis. Retinal pigment epithelial cells (RPECs) were cultured with IL-1β and fenofibrate ranging from 1-50 μM. ENA-78, IL-8, and RANTES were measured in cell culture by ELISA...
December 20, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27981812/take-care-of-the-fast-in-human-study
#8
Ewoud-Jan Hoogdalem
Drug developers often evaluate products with unprecedented mechanism of action under pressure to bring products to patients fast. The recent tragedy with a fatty-acid amide hydrolase inhibitor raises questions on balancing good science and good business while safeguarding safety and ethical standards. Was the issue with processing information rather than data package? Full disclosure and root cause analysis are called for. Recommendations are made to ensure integration of preclinical learning with the clinical plan...
December 16, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27981790/tlr4-and-caveolin-1-in-monocytes-are-associated-with-inflammatory-conditions-in-diabetic-neuropathy
#9
T Zhu, Q Meng, J Ji, L Zhang, X Lou
The purpose of this study was to investigate the expression of TLR4 and caveolin-1 in monocytes among healthy volunteers as well as those with type-2 diabetes mellitus (T2DM) and diabetic peripheral neuropathy (DPN). Nineteen healthy control subjects, 18 patients with T2DM, and 20 patients with DPN were enrolled. Toll-like receptor (TLR)4, caveolin-1, MyD88, phosphorylated IκB, and plasma TNF-α and interleukin (IL)-6 were measured using real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay...
December 16, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27925405/animal-to-human-dose-translation-of-obiltoxaximab-for-treatment-of-inhalational-anthrax-under-the-us-fda-animal-rule
#10
C F Nagy, J Mondick, N Serbina, L S Casey, S E Carpenter, J French, R Guttendorf
Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax under the US Food and Drug Administration's (FDA) Animal Rule. The human dose was selected and justified by comparing observed obiltoxaximab exposures in healthy and infected New Zealand White rabbits and cynomolgus macaques to observed exposures in healthy humans, to simulated exposures in healthy and infected humans, and to serum PA levels in infected animals. In humans, at 16 mg/kg intravenous, obiltoxaximab AUC was >2 times that in animals, while maximum serum concentrations were comparable to those in animals and were maintained in excess of the concentration required for PA neutralization in infected animals for 2-3 weeks...
December 7, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27860267/a-phase-i-randomized-study-of-a-specifically-engineered-ph-sensitive-pcsk9-inhibitor-rn317-pf-05335810-in-hypercholesterolemic-subjects-on-statin-therapy
#11
M Levisetti, T Joh, H Wan, H Liang, P Forgues, B Gumbiner, P D Garzone
This phase I study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of RN317 (PF-05335810), a specifically engineered, pH-sensitive, humanized proprotein convertase subtilisin kexin type 9 (PCSK9) monoclonal antibody, in hypercholesterolemic subjects (low-density lipoprotein cholesterol (LDL-C) ≥ 80 mg/dl) 18-70 years old receiving statin therapy. Subjects were randomized to: single-dose placebo, RN317 (subcutaneous (s.c.) 0.3, 1, 3, 6, or intravenous (i.v.) 1, 3, 6 mg/kg), or bococizumab (s...
November 17, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27863029/endoluminal-vacuum-therapy-for-ivor-lewis-anastomotic-leaks-a-pilot-study-in-a-swine-model
#12
R B Scott, L A Ritter, A L Shada, S H Feldman, D E Kleiner
Anastomotic leaks are a serious complication associated with Ivor Lewis esophagectomies. Endoluminal negative pressure vacuum devices create a possible treatment alternative to conventional surgical intervention. Ten pigs had an intrathoracic esophageal anastomosis with a 1-cm defect. The experimental group had the device placed intraoperatively across the defect, whereas the control group did not. Once treatment was completed, a contrast fluoroscopic study and necropsy was performed. All control pigs had contrast extravasation on fluoroscopy and contamination on necropsy...
November 11, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27991741/4%C3%AE-hydroxycholesterol-level-in-patients-with-rheumatoid-arthritis-before-vs-after-initiation-of-bdmards-and-correlation-with-inflammatory-state
#13
B M Wollmann, S W Syversen, E Lie, C Gjestad, L L Mehus, I C Olsen, E Molden
Systemic inflammation has been linked to suppressed CYP3A(4) activity. We determined 4β-hydroxycholesterol (4βOHC), an endogenous CYP3A4 metabolite, in patients with rheumatoid arthritis (RA) before and after treatment with biological disease-modifying antirheumatic drugs (bDMARDs). The 4βOHC was compared in 41 patients before and 2-5 months after initiating TNFα inhibitors (n = 31), IL-6 inhibitors (n = 5), or B-cell inhibitors (n = 5). Correlations between 4βOHC and inflammatory markers (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) were also tested before and after bDMARDs...
November 5, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27806191/phase-1-studies-of-acebilustat-biomarker-response-and-safety-in-patients-with-cystic-fibrosis
#14
J S Elborn, A Horsley, G MacGregor, D Bilton, R Grosswald, S Ahuja, E B Springman
There is a significant unmet need for safe and effective anti-inflammatory treatment for cystic fibrosis. The aim of this study was to evaluate the safety of acebilustat, a leukotriene A4 hydrolase inhibitor, and its effect on inflammation biomarkers in patients with cystic fibrosis. Seventeen patients with mild to moderate cystic fibrosis were enrolled and randomized into groups receiving placebo or doses of 50 mg or 100 mg acebilustat administered orally, once daily for 15 days. Sputum neutrophil counts were reduced by 65% over baseline values in patients treated with 100 mg acebilustat...
November 2, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27792868/phase-i-studies-of-acebilustat-pharmacokinetics-pharmacodynamics-food-effect-and-cyp3a-induction
#15
J S Elborn, L Bhatt, R Grosswald, S Ahuja, E B Springman
Acebilustat is a new once-daily oral antiinflammatory drug in development for treatment of cystic fibrosis (CF) and other diseases. It is an inhibitor of leukotriene A4 hydrolase; therefore, production of leukotriene B4 (LTB4) in biological fluids provides a direct measure of the pharmacodynamic (PD) response to acebilustat treatment. Here we compare the pharmacokinetics (PK) and PD between CF patients and healthy volunteers, and investigate the food effect and CYP3A4 induction in healthy volunteers. No significant differences between study populations were observed for peak plasma level (Cmax ) or exposure (AUC)...
October 28, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27785887/exploration-of-biomarkers-for-amoxicillin-clavulanate-induced-liver-injury-multi-omics-approaches
#16
J Lee, S C Ji, B Kim, S Yi, K H Shin, J Y Cho, K S Lim, S H Lee, S H Yoon, J Y Chung, K S Yu, H S Park, S H Kim, I J Jang
To explore potential biomarkers for amoxicillin/clavulanate-induced liver injury (AC-DILI), we conducted a clinical trial in 32 healthy subjects based on multi-omics approaches. Every subject was administered amoxicillin/clavulanate for 14 days. The liver-specific microRNA-122 (miR-122) level increased prior to and correlated well with the observed alanine aminotransferase (ALT) level increase. This result indicates its potential as a sensitive early marker for AC-DILI. We also identified urinary metabolites, such as azelaic acid and 7-methylxanthine, with levels that significantly differed among the groups classified by ALT elevation level on day 8 after drug administration (P < 0...
October 26, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27860319/the-role-of-next-generation-sequencing-in-enabling-personalized-oncology-therapy
#17
C A Cummings, E Peters, L Lacroix, F Andre, M R Lackner
No abstract text is available yet for this article.
December 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27766744/pttg1-levels-are-predictive-of-saracatinib-sensitivity-in-ovarian-cancer-cell-lines
#18
I Nakachi, B A Helfrich, M A Spillman, E A Mickler, C J Olson, J L Rice, C D Coldren, L E Heasley, M W Geraci, R S Stearman
Src kinase is recognized as a key target for molecular cancer therapy. However, methods to efficiently select patients responsive to Src inhibitors are lacking. We explored the sensitivity of ovarian cancer cell lines to the Src kinase inhibitor saracatinib to identify predictive markers of drug sensitivity using gene microarrays. Pituitary tumor transforming gene 1 (PTTG1) was selected as a potential biomarker as mRNA levels were correlated with saracatinib resistance, as well as higher PTTG1 protein expression...
December 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27754602/population-pharmacokinetics-of-methylphenidate-in-healthy-adults-emphasizing-novel-and-known-effects-of-several-carboxylesterase-1-ces1-variants
#19
Y K Lyauk, C Stage, T K Bergmann, L Ferrero-Milliani, D Bjerre, R Thomsen, K P Dalhoff, H B Rasmussen, G Jürgens
The aim of this study was to identify demographic and genetic factors that significantly affect methylphenidate (MPH) pharmacokinetics (PK), and may help explain interindividual variability and further increase the safety of MPH. d-MPH plasma concentrations, demographic covariates, and carboxylesterase 1 (CES1) genotypes were gathered from 122 healthy adults and analyzed using nonlinear mixed effects modeling. The structural model that best described the data was a two-compartment disposition model with absorption transit compartments...
December 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27743502/modeling-and-experimental-studies-of-obeticholic-acid-exposure-and-the-impact-of-cirrhosis-stage
#20
J E Edwards, C LaCerte, T Peyret, N H Gosselin, J F Marier, A F Hofmann, D Shapiro
Obeticholic acid (OCA), a semisynthetic bile acid, is a selective and potent farnesoid X receptor (FXR) agonist in development for the treatment of chronic nonviral liver diseases. Physiologic pharmacokinetic models have been previously used to describe the absorption, distribution, metabolism, and excretion (ADME) of bile acids. OCA plasma levels were measured in healthy volunteers and cirrhotic subjects. A physiologic pharmacokinetic model was developed to quantitatively describe the ADME of OCA in patients with and without hepatic impairment...
December 2016: Clinical and Translational Science
journal
journal
41994
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"