A5003486139- Biosimilars and Bioanalytical Methods
- Chemical Reactions and Isotopes
- Metabolomics and Mass Spectrometry Studies
- Pharmaceutical studies and practices
- Asthma and respiratory diseases
- Pharmacogenetics and Drug Metabolism
- Mass Spectrometry Techniques and Applications
- Antibiotics Pharmacokinetics and Efficacy
- Inhalation and Respiratory Drug Delivery
- Computational Drug Discovery Methods
- Analytical Chemistry and Chromatography
- Drug Transport and Resistance Mechanisms
- Respiratory and Cough-Related Research
- Erythropoietin and Anemia Treatment
- Metabolism and Genetic Disorders
- Pharmacological Effects and Toxicity Studies
- Colorectal Cancer Treatments and Studies
- Protein purification and stability
- Cell Image Analysis Techniques
- Melanoma and MAPK Pathways
- Isotope Analysis in Ecology
- Synthesis and biological activity
- Carcinogens and Genotoxicity Assessment
- Mitochondrial Function and Pathology
- Analytical Methods in Pharmaceuticals
GlaxoSmithKline (United Kingdom)
2013-2024
University of Hertfordshire
2000-2023
Age UK
2022-2023
GlaxoSmithKline (United States)
2013-2022
Covance (United Kingdom)
2019-2021
Hammersmith Medicines Research
2019-2021
GlaxoSmithKline (Australia)
2019
University of Oxford
2017
Research Triangle Park Foundation
2013
Zimmer Biomet (United Kingdom)
2000
The 5th Workshop on Recent Issues in Bioanalysis (WRIB) was organized by the Calibration and Validation Group as a 2-day full immersion workshop for pharmaceutical companies, CROs regulatory agencies to discuss, review, share perspectives, provide potential solutions agree upon consistent approach recent issues bioanalysis of both small large molecules. High quality, better compliance regulations scientific excellence are foundation this workshop. As previous editions significant event,...
The metabolism and disposition of vilanterol, a novel long-acting <i>β</i><sub>2</sub>-adrenoceptor agonist (LABA) for inhalation use, was investigated after oral administration in humans. Single administrations up to 500 <i>μ</i>g vilanterol were shown be safe well tolerated two clinical studies healthy men. In human radiolabel study, six men received single dose 200 [<sup>14</sup>C]vilanterol (74 kBq). Plasma, urine, feces collected 168 hours the analyzed metabolites, radioactivity. At...
Human radiolabel studies are traditionally conducted to provide a definitive understanding of the human absorption, distribution, metabolism and excretion (ADME) properties drug. However, advances in technology over past decade have allowed alternative methods be employed obtain both clinical ADME pharmacokinetic (PK) information. These include microdose microtracer approaches using accelerator mass spectrometry, identification quantification metabolites samples from classical PK...
The CC-chemokine receptor 4 (CCR4) is thought potentially to play a critical role in asthma pathogenesis due its ability recruit type 2 T-helper lymphocytes the inflamed airways. Therefore, CCR4 provides an excellent target for anti-inflammatory therapy. safety, tolerability, pharmacokinetics and pharmacodynamics of antagonist GSK2239633, N-(3-((3-(5-chlorothiophene-2-sulfonamido)-4-methoxy-1H-indazol-1-yl)methyl)benzyl)-2-hydroxy-2-methylpropanamide, were examined healthy males. Two studies...
The aim of this phase 1, single centre, open label study in four patients with solid tumours was to determine the absolute bioavailability a 2 mg oral dose trametinib. Trametinib is an orally bioavailable, reversible and selective allosteric inhibitor MEK1 MEK2 activation kinase activity.A microtracer approach, which 5 μg radiolabelled i.v. microdose trametinib given concomitantly unlabelled tablet formulation, used recover pharmacokinetic parameters, simultaneously.The least-squares mean...
The human absorption, distribution, metabolism, and excretion (hADME) study is the cornerstone of clinical pharmacology package for small molecule drugs, providing comprehensive information on rates routes disposition elimination drug-related material in humans through use
Abstract Dabrafenib is an orally bioavailable, potent, and selective inhibitor of human wild‐type BRAF CRAF kinases as well mutant forms kinase. The aim this phase 1, single‐center, open‐label study in four patients with mutation‐positive solid tumors was to determine the absolute bioavailability a 150 mg oral dose dabrafenib. A microtracer approach, which 50 µg radiolabeled intravenous (IV) microdose dabrafenib given concomitantly dose, used simultaneously recover IV pharmacokinetic...
1. The technique of accelerator mass spectrometry (AMS) is outlined. 2. use AMS in an initial validation study animals As part the technique, samples from animal were analysed by both liquid scintillation counting (LSC) and, following dilution, AMS. results similar. 3. support a clinical described. Six healthy male human volunteers administered 2.7mg [14
Accelerator mass spectrometry (AMS) is being used more widely to provide PK data for early decision making or generate absolute bioavailability in later phases of development. Presently, there no clear consensus on the level scientific validation required these assays. The European Bioanalysis Forum (EBF) has conducted two surveys with its members and presented results at 4th Open Symposium. With AMS discrete assessment, method establishment assays should focus science rather than trying fit...
Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition, causing progressive decline in function leading to premature death. Acute exacerbations COPD patients are predominantly associated with respiratory viruses. Ribavirin a generic broad-spectrum antiviral agent that could be used for treatment of viral infections COPD. Using the Particle Replication In Nonwetting Templates (PRINT) technology, which produces dry-powder particles uniform shape and size, two new...
Abstract The introduction of ‘compact’ accelerator mass spectrometers into biomedical science, including use in drug metabolism and bioanalytical applications, is an exciting recent development. Comparisons are presented here between a more established relatively large tandem which operates at up to 5 MV conventional laboratory‐sized 250 kV single‐stage spectrometer. Biological samples were enriched with low levels radiocarbon, then converted graphite prior analysis on each the two...
Metabolite quantification and profiling continues to grow in importance today's drug development. The guidance provided by the 2008 FDA Metabolites Safety Testing Guidance subsequent ICH M3(R2) (2009) has led a more streamlined process assess metabolite exposures preclinical clinical studies industry. In addition, European Bioanalysis Forum (EBF) identified an opportunity refine strategies on considering experience date with their recommendation paper subject dating from 2010 integrating...
(S)-3-(Aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole (GSK2251052) is a novel boron-containing antibiotic that inhibits bacterial leucyl tRNA synthetase, and has been in development for the treatment of serious Gram-negative infections. In this study, six healthy adult male subjects received single i.v. dose [<sup>14</sup>C]GSK2251052, 1500 mg infused over 1 hour. Blood, urine, feces were collected an extended period 14 days, accelerator mass spectrometry was used...
An innovative open-label, crossover clinical study was used to investigate the excretion balance, pharmacokinetics, and metabolism of nemiralisib—an inhaled phosphoinositide 3-kinase delta inhibitor being developed for respiratory diseases. Six healthy men received a single intravenous microtracer 10 <i>µ</i>g [<sup>14</sup>C]nemiralisib with concomitant nonradiolabeled 1000 dose followed by an oral 800 14 days later. Complementary methods including accelerator mass spectrometry allowed...
<h3>Objective</h3> We investigated the contribution of small vessel disease (SVD) to anticoagulant-associated intracerebral haemorrhage (ICH). <h3>Methods</h3> Clinical Relevance Microbleeds in Stroke-2 comprised two independent multicentre observation studies: first, a cross-sectional study patients with ICH; and second, prospective taking anticoagulants for atrial fibrillation (AF) after cerebral ischaemia. In ICH, we compared SVD markers on CT MRI according prior anticoagulant therapy. AF...
The absorption, metabolism, and excretion of darapladib, a novel inhibitor lipoprotein-associated phospholipase A<sub>2</sub>, was investigated in healthy male subjects using [<sup>14</sup>C]-radiolabeled material bespoke study design. Disposition darapladib compared following single i.v. both repeated oral administrations. anticipated presence low circulating concentrations drug-related required the use accelerator mass spectrometry as sensitive radiodetector. Blood, urine, feces were...
Phase 0 approaches, including microdosing, involve the use of sub-therapeutic exposures to tested drugs, thus enabling safer, more-relevant, quicker and cheaper first-in-human (FIH) testing. These approaches also have considerable potential limit animals in human drug development. Recent years witnessed progress applications, methodology, operations, development culture. Advances applications saw an expansion therapeutic areas, developmental scenarios scientific objectives, in, for example,...
Linerixibat, an oral small-molecule ileal bile acid transporter inhibitor under development for cholestatic pruritus in primary biliary cholangitis, was designed minimal absorption from the intestine (site of pharmacological action). This study characterized pharmacokinetics, absorption, metabolism, and excretion [<sup>14</sup>C]-linerixibat humans after intravenous microtracer concomitant with unlabeled tablets solution. Linerixibat exhibited absorption-limited flip-flop kinetics: longer...
Abstract Daprodustat, an oral hypoxia‐inducible factor prolyl hydroxylase inhibitor, is being investigated for treatment of anemia in chronic kidney disease. This phase 1, nonrandomized, 2‐period, crossover study 6 healthy men characterized the absorption, distribution, and excretion daprodustat when administered as intravenous (IV) doses unlabeled radiolabeled ([ 14 C]‐GSK1278863). Tolerability pharmacokinetic properties daprodustat, its metabolites systemic circulation, were also...