A5042403500- Microfluidic and Capillary Electrophoresis Applications
- Analytical Chemistry and Chromatography
- Innovative Microfluidic and Catalytic Techniques Innovation
- Microfluidic and Bio-sensing Technologies
- Mass Spectrometry Techniques and Applications
- Pharmacogenetics and Drug Metabolism
- Hemophilia Treatment and Research
- Radiopharmaceutical Chemistry and Applications
- Diabetes Treatment and Management
- Metabolomics and Mass Spectrometry Studies
- Chemical Synthesis and Analysis
- Peptidase Inhibition and Analysis
- Electrowetting and Microfluidic Technologies
- Pharmaceutical studies and practices
- Analytical Chemistry and Sensors
- Inhalation and Respiratory Drug Delivery
- Forensic Toxicology and Drug Analysis
- Pain Mechanisms and Treatments
- Metabolism and Genetic Disorders
- Cannabis and Cannabinoid Research
- Medical Imaging Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Pain Management and Opioid Use
- Neuroendocrine Tumor Research Advances
- Chemical Reactions and Isotopes
Novo Nordisk (Denmark)
2009-2024
University of California, San Francisco
2005
Schools of Visual Arts, The Royal Danish Academy of Fine Arts
1995-2001
GlaxoSmithKline (United Kingdom)
2001
Aims To identify the principal human cytochrome P450 (CYP) enzyme(s) responsible for in vitro biotransformation of repaglinide. Previous experiments have identified CYP3A4 as being mainly metabolism repaglinide, but results clinical investigations suggested that more than one enzyme may be involved repaglinide biotransformation. Methods [ 14 C]‐Repaglinide was incubated with recombinant CYP and liver microsomes (HLM) from individual donors presence inhibitory antibodies specific enzymes....
Liraglutide is a novel once-daily human glucagon-like peptide (GLP)-1 analog in clinical use for the treatment of type 2 diabetes. To study metabolism and excretion [<sup>3</sup>H]liraglutide, single subcutaneous dose 0.75 mg/14.2 MBq was given to healthy males. The recovered radioactivity blood, urine, feces measured, metabolites were profiled. In addition, [<sup>3</sup>H]liraglutide [<sup>3</sup>H]GLP-1(7–37) incubated vitro with dipeptidyl peptidase-IV (DPP-IV) neutral endopeptidase (NEP)...
Semaglutide is a human glucagon-like peptide-1 analogue in clinical development for the treatment of type 2 diabetes. The absorption, metabolism and excretion single 0.5mg/450μCi [16.7MBq] subcutaneous dose [3H]-radiolabelled semaglutide was investigated healthy subjects compared with data from nonclinical studies. Radioactivity blood, plasma, urine faeces determined humans, rats monkeys; radioactivity expired air humans rats. Metabolites were quantified following profiling radiodetection....
The on-line separation and structure elucidation of naphthodianthrones, flavonoids, other constituents an extract from Hypericum perforatum L. using high performance liquid chromatography (HPLC) coupled with ultraviolet−visible, nuclear magnetic resonance (NMR), mass spectrometry (MS) is described. A conventional reversed-phase HPLC system ammonium acetate as the buffer substance in eluent was used, proton NMR spectra were obtained on a 500 MHz instrument. MS MS/MS analyses performed...
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
The hypoalgesic effect of single oral doses 100 mg imipramine and 125 codeine was evaluated in a randomised, placebo-controlled, double-blind, 3-way cross-over experiment including 18 healthy volunteers. Pain tests were performed before 90, 180, 270, 360 450 min after medication. included determination pain tolerance thresholds to pressure, detection/tolerance electrical sural nerve stimulation summation at threshold repetitive (temporal summation) experienced during the cold pressor test,...
Zomepirac [ZP, 5-(chlorobenzoyl)-1,4-dimethylpyrrole-2-acetic acid] was withdrawn from the market because of unpredictable allergic reactions that may have been caused by ZP−protein adducts formed reaction reactive acyl glucuronide ZP (ZP-O-G) with endogenous proteins. To test hypothesis coenzyme A thioester (ZP-CoA) and potentially could contribute to formation adducts, we investigated CoA-dependent metabolism in freshly isolated rat hepatocytes (1 mM) vivo (100 mg ZP/kg, ip) livers (2 h...
Carboxylic acids may be metabolized to acyl glucuronides and acyl-coenzyme A thioesters (acyl-CoAs), which are reactive metabolites capable of reacting with proteins in vivo. In this study, the metabolic activation tolmetin (Tol) subsequent formation Tol-protein adducts liver were studied rats. Two hours after dose administration (100 mg/kg i.p.), acyl-CoA (Tol-CoA) was identified by liquid chromatography-tandem mass spectrometry homogenates. Similarly, acyl-CoA-dependent tolmetin-taurine...
The biologic fate of the [3H]PEG-moiety incorporated into N8-GP was evaluated based on single i.v. bolus doses to rats. Furthermore, 40 kDa given separately rats by doses, investigate if pharmacokinetics were dose-dependent. For both compounds, plasma pharmacokinetics, distribution and excretion pathways investigated, total radioactivity measurements ([3H]N8-GP: 0.17–4.1 mg/kg;~1300–30,000 U/kg, PEG load ~ 0.03–0.7 mg/kg); ([3H]PEG: 0.6, 1, 12, 100 200 mg/kg). concentration intact conjugate...
Positron emission tomography (PET) imaging is used in drug development to noninvasively measure biodistribution and receptor occupancy. Ideally, PET tracers retain target binding properties of the investigated drug. Previously, we developed a zirconium-89 tracer based on long-circulating glucagon-like peptide 1 agonist (GLP-1RA) using desferrioxamine (DFO) as chelator. Here, aimed develop an improved zirconium-89-labeled GLP-1RA with increased molar activity increase uptake low density...
Nonacog beta pegol (N9-GP) is a novel recombinant factor IX conjugated with 40-kDa branched polyethylene glycol (PEG) to extend plasma half-life (t½) compared native FIX, developed for the treatment of haemophilia B. This first time distribution, metabolism, and excretion data N9-GP have been presented. ADME studies were performed using single i.v. doses radiolabelled administered rats, focussing on biological fate PEG. Results indicated that N9-GP-related radioactivity was distributed...
Abstract A capillary electrophoresis method for determination of the enantiomers ibuprofen and its major phase I metabolites: 2′‐hydroxyibuprofen 2′‐carboxyibuprofen in urine samples have been developed. Cyclodextrins linear dextrins investigated as chiral selectors. Simultaneous separation ibuprofen, was obtained using a mixture dextrin 10 heptakis (2,3,6‐tri‐ O ‐methyl)‐β‐cyclodextrin 2‐[ N ‐morpholino]ethanesulphonic acid buffer, pH 5.26. The electroosmotic flow reversed hexadimethrine...
Disorders in lipoprotein metabolism are critical the etiology of several disease states such as coronary heart and atherosclerosis. Thus, there is considerable interest development novel methods for analysis complexes. We report here a simple chromatographic method separation high-density lipoprotein, low-density very from intact serum or plasma. The was achieved using hydroxyapatite column elution with pH 7.4 phosphate buffer 100-μL injections whole Coelution HDL plasma proteins albumin...