A5047335736- Potassium and Related Disorders
- Advanced Chemical Physics Studies
- Electrolyte and hormonal disorders
- Magnesium in Health and Disease
- Mass Spectrometry Techniques and Applications
- Atomic and Molecular Physics
- Gastroesophageal reflux and treatments
- Atmospheric chemistry and aerosols
- Pharmacogenetics and Drug Metabolism
- Atmospheric Ozone and Climate
- Pharmacological Effects and Toxicity Studies
- Hemoglobinopathies and Related Disorders
- Spectroscopy and Quantum Chemical Studies
- PI3K/AKT/mTOR signaling in cancer
- SARS-CoV-2 and COVID-19 Research
- Quantum, superfluid, helium dynamics
- Analytical Chemistry and Chromatography
- Spectroscopy and Laser Applications
- Neonatal Health and Biochemistry
- Diabetes Treatment and Management
- Electrochemical Analysis and Applications
- Membrane-based Ion Separation Techniques
- Advanced Breast Cancer Therapies
- Statistical Methods in Clinical Trials
- Receptor Mechanisms and Signaling
AstraZeneca (United States)
2019-2024
AstraZeneca (Brazil)
2015-2024
Quantitative BioSciences
2023
AstraZeneca (Sweden)
2003-2019
University of Gothenburg
1998-2007
Stockholm University
2004
AstraZeneca (United Kingdom)
2002
University of Borås
2000
Dissociative recombination of the polyatomic ions D3O+ and H3O+ with electrons have been studied at heavy-ion storage ring CRYRING (Manne Siegbahn Laboratory, Stockholm University). Absolute cross sections determined from 0.001 eV to 0.25 center-of-mass energy for 28 H3O+. The are large (7.3×10−13 cm2 3.3×10−12 eV). At low energies, E−1 dependent whereas it is slightly steeper A similar dependence was also observed by Mul et al. [J. Phys. B 16, 3099 (1983)] a merged electron-ion beam...
A high-throughput pKa screening method based on pressure-assisted capillary electrophoresis (CE) and mass spectrometry (MS) is presented. Effects of buffer type ionic strength sensitivity values were investigated. Influence dimethyl sulfoxide (DMSO) concentration present in the sample effective mobility measurement was examined. series ten volatile buffers, covering a pH range from 2.5 to 10.5 with same strength, employed. The application background electrolytes resulted significant signal...
The mechanism behind the glucose lowering effect occurring after specific activation of GPR120 is not completely understood. In this study, a potent and selective agonist was developed its pharmacological properties were compared with previously described Metabolex-36. Effects both compounds on signaling pathways GLP-1 secretion investigated in vitro. acute studied lean wild-type null mice following oral or intravenous tolerance tests. vitro, overexpressing cells, agonists signaled through...
ABSTRACT AZD7442 is a combination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies, tixagevimab and cilgavimab, developed for pre-exposure prophylaxis (PrEP) treatment disease 2019 (COVID-19). Using data from eight clinical trials, we describe population pharmacokinetic (popPK) model show how modeling “interim” accelerated decision-making during the COVID-19 pandemic. The final was two-compartmental distribution with first-order absorption elimination,...
Objectives: atazanavir has been reported to increase total bilirubin (TB) level up 9-fold [1]. It is widely believed that the observed TB elevation primarily due UGT1A1 inhibition. However, OATP1B1/3 may contribute interaction as a potent inhibitor and hepatic uptake of both UB conjugated (CB) are mediated by them [2]. The objective this study was develop physiologically based pharmacokinetic (PBPK) models quantitatively understand contribution interaction.Methods: All PBPK modeling...
5-Lipoxygenase activating protein (FLAP) inhibitors attenuate 5-lipoxygenase pathway activity and reduce the production of proinflammatory vasoactive leukotrienes. As such, they are hypothesized to have therapeutic benefit for treatment diseases that involve chronic inflammation including coronary artery disease. Herein, we disclose medicinal chemistry discovery early clinical development FLAP inhibitor AZD5718 (12). Multiparameter optimization included securing adequate potency in human...
The dissociative recombination (DR) process of NH4+ and ND4+ molecular ions with free electrons has been studied at the heavy-ion storage ring CRYRING (Manne Siegbahn Laboratory, Stockholm University). absolute cross sections for DR in collision energy range 0.001–1 eV are reported, thermal rate coefficients temperature interval from 10 to 2000 K calculated experimental data. section agrees well earlier work is about a factor 2 larger than ND4+. dominated by product channels NH3+H...
The dynamics of HCl collisions with ice surfaces is studied using molecular beam techniques. experiments are carried out a water vapor pressure up to 3 × 10-5 mbar outside the surface, which allows be performed at surface temperatures 127−180 K. At higher temperatures, has very dynamic character and constantly undergoes evaporation condensation. Angular-resolved intensity time-of-flight distributions measured mass spectrometry, effects temperature, incident kinetic energy, coverage...
Abstract Objectives The evolution of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) necessitates rapid methods for assessing monoclonal antibody (mAb) potency against emerging variants. Authentic virus neutralisation assays are considered the gold standard measuring virus‐neutralising (nAb) titres in serum. However, authentic virus‐based pose inherent practical challenges nAb SARS‐CoV‐2 variants (e.g. storing infectious viruses and testing at biosafety level‐3 facilities)....
Dissociative recombination (DR) of the water cluster ion D+(D2O)2 has been studied at heavy-ion storage ring CRYRING (Manne Siegbahn Laboratory, Stockholm University). Cluster ions were injected into and accelerated to an energy 2.28 MeV. The stored beam was merged with almost monoenergetic electron beam, neutral fragments produced by DR detected energy-sensitive surface barrier detector. first experimental determinations absolute cross section branching ratios for a are reported. process...
The dynamics of argon atom collisions with water ice at 110−180 K is investigated using molecular beam experiments and simulations. Initial energies 0.065 to 0.93 eV incident angles 0 70° are used, directly scattered thermally desorbed atoms separated by angular-resolved time-of-flight measurements. For thermal the scattering almost entirely due trapping followed desorption. higher direct inelastic observed, channel favored a high initial energy, large angle surface temperature. Results from...
A different drug-drug interaction (DDI) scenario may exist in patients with chronic kidney disease (CKD) compared healthy volunteers (HVs), depending on the interplay between and (drug-drug-disease (DDDI)). Physiologically-based pharmacokinetic (PBPK) modeling, lieu of a clinical trial, is promising tool for evaluating these complex DDDIs patients. However, prediction confidence PBPK modeling severe CKD population still low when nonrenal pathways are involved. More mechanistic virtual robust...
We report on molecular beam experiments and dynamics simulations of xenon scattering with incident energies E=0.06−5.65 eV from graphite. The corrugation felt by an atom interacting the surface is found to be influenced both temperature, Ts, E. Angular distributions are significantly broadened when Ts increased, clearly indicating induced thermal motion also at highest E employed. Direct dominates for high E, while trapping becomes important kinetic below 1 eV. coupling between translation...
Dapagliflozin is an inhibitor of human renal sodium‐glucose cotransporter 2 (SGLT2), first approved for the treatment type diabetes mellitus (T2DM). primarily metabolized by uridine diphosphate glucuronosyltransferase 1A9 (UGT1A9). The effect UGT1A9 polymorphisms on dapagliflozin apparent oral clearance (CL/F) was studied with population pharmacokinetic data and genotype (I.399C>T, rs2011404, rs6759892, rs7577677, rs4148323, UGT1A9*2 UGT1A9*3) from a Phase study conducted in subjects T2DM...
Carbon dioxide interactions with crystalline and amorphous water ice have been studied by time-resolved molecular beam techniques. CO2 collisions at thermal kinetic energies in the temperature range 100−160 K result efficient trapping on surface followed desorption. The desorption kinetics 100−125 are well described Arrhenius equation an activation energy of 0.22 ± 0.02 eV a preexponential factor 1013.32±0.57 s-1. Below 120 K, populates strongly bonded sites ice, resulting residence times...
The in vitro metabolic stability assays are indispensable for screening the liability of new chemical entities (NCEs) drug discovery. Intrinsic clearance (CLint) values from liver microsomes and/or hepatocytes frequently used to assess as well quantitatively predict vivo hepatic plasma (CLH). An often approximation is so called wellstirred model which has gained widespread use. applications well-stirred typically dependent on several measured parameters and hence with potential...
Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism for gastroesophageal reflux. Characterizations of candidate compounds reduction TLESRs are traditionally done through summary exposure and response measures would benefit from model-based analyses exposure-TLESR events relationships. Pharmacokinetic (PK)-pharmacodynamic (PD) modeling approaches treating either as count data or repeated time-to-event (RTTE) were developed compared in terms their ability to...
Dissociative recombination (DR) of the water cluster ions H+(H2O)3 and D+(D2O)3 with electrons has been studied at heavy-ion storage ring CRYRING (Manne Siegbahn Laboratory, Stockholm University). For first time, absolute DR cross sections have measured for in energy range 0.001–0.8eV, relative 0.001–1.0eV. The are larger than previously observed H+(H2O)n (n=1,2), which is agreement trend indicating that rate coefficient increases size ion. Branching ratios determined dominating product...
Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a potassium (K+) binder for treatment of hyperkalemia in adults. SZC binds K+ exchange sodium (Na+) or hydrogen (H+) the gastrointestinal tract, conveying potential systemic absorption Na+.This single-center Phase 1 study evaluated effects on Na+ and excretion healthy, normokalemic During an initial run-in period (Days 1-2), participants started high K+/low diet. After baseline 3-4), SCZ 5 10 g once daily (QD) was administered 5-8). The...
Abstract Purpose To support future dosing recommendations, the effect of food on pharmacokinetics adavosertib, a first-in-class, small-molecule reversible inhibitor WEE1 kinase, was assessed in patients with advanced solid tumors. Methods In this Phase I, open-label, randomized, two-period, two-sequence crossover study, single 300 mg adavosertib dose were investigated fed versus fasted states. Results Compared state, high-fat, high-calorie meal (fed state) decreased maximum plasma...