A5037657912- Pharmacogenetics and Drug Metabolism
- Veterinary Pharmacology and Anesthesia
- Pharmacological Effects and Assays
- Chemical Reaction Mechanisms
- Drug Transport and Resistance Mechanisms
- Receptor Mechanisms and Signaling
- Asthma and respiratory diseases
- Computational Drug Discovery Methods
- Veterinary Equine Medical Research
- Analytical Chemistry and Chromatography
- Cyclopropane Reaction Mechanisms
- Chemical Reactions and Mechanisms
- Synthesis and Biological Evaluation
- Antibiotics Pharmacokinetics and Efficacy
- Inhalation and Respiratory Drug Delivery
- Drug-Induced Hepatotoxicity and Protection
- Hormonal and reproductive studies
- Chemical Synthesis and Analysis
- Inflammatory mediators and NSAID effects
- Organic Chemistry Cycloaddition Reactions
- Muscle metabolism and nutrition
- Adrenal Hormones and Disorders
- Radical Photochemical Reactions
- Analytical Methods in Pharmaceuticals
- Liver physiology and pathology
University of Nottingham
2016-2025
Nottingham College
2013-2016
Loughborough University
2004-2014
AstraZeneca (United Kingdom)
2004-2014
AstraZeneca (Sweden)
2012
British Horseracing Authority
2012
Wake Forest University
2006-2012
AstraZeneca (Brazil)
2007-2011
University of Toronto
1996-2005
The disposition of atorvastatin, cerivastatin, and indomethacin, established substrates rat hepatic basolateral uptake transporters, has been evaluated in suspended hepatocytes. Cell media concentration-time data were simultaneously fitted to a model incorporating active uptake, permeation, binding, metabolism. Use the estimate ratio intracellular extracellular steady-state free drug concentrations demonstrated strong influence on kinetics atorvastatin (18:1) cerivastatin (8:1), comparison...
Identifying any extrahepatic excretion phenomenon in preclinical species is crucial for an accurate prediction of the pharmacokinetics man. This understanding particularly key drugs with a small volume distribution, because they require especially low total clearance to be suitable once-a-day dosing regimen In this study, three animal scaling techniques were applied human renal 36 diverse that show active secretion or net reabsorption: 1) direct correlations between man and each two main...
Omeprazole is a gastric acid secretion inhibitor used as an effective anti-ulcer drug. Based on oral administration studies, its International Screening Limit (ISL) was established in plasma and urine at 1 ng/mL with Detection Time (DT) of 48 h. A novel formulation injectable omeprazole has since been released, therefore, pharmacokinetic study performed to assess the DT above ISL against current advice. Six Thoroughbred horses were given four repeated weekly intramuscular administrations (4...
We present herein a QSAR tool enabling an entirely in silico prediction of human and rat steady-state volume distribution (Vss), to be made prior chemical synthesis, preceding detailed allometric or mechanistic assessment Vss. Three different statistical methodologies, Bayesian neural networks (BNN), classification regression trees (CART), partial least squares (PLS) were employed model (N=199) (N=2086) data sets. The results independent test set show the has r2 0.60 rms error 0.48....
QSAR models for a diverse set of compounds cytochrome P450 1A2 inhibition have been produced using 4 statistical approaches; partial least squares (PLS), multiple linear regression (MLR), classification and trees (CART), bayesian neural networks (BNN). The complement one another identified the following descriptors as important features CYP1A2 inhibition; lipophilicity, aromaticity, charge, HOMO/LUMO energies. Furthermore all are global used to predict independent compounds. For first time...
From a search of the available literature, database 22 drugs all charge types and several different therapeutic classes was compiled to compare rat human biliary clearance data. Dog excretion data were also found for nine drugs. For 19 (86%), unbound values, when normalized body weight, exceeded those humans by factors ranging from 9 over 2500-fold, whereas human/dog differences much less dramatic. It possible define hepatic uptake efflux transporter involvement many On basis findings, it is...
Typically, inhaled drugs are rapidly absorbed into the bloodstream, which results in systemic side effects and a brief residence time lungs. PEGylation was evaluated as novel strategy for prolonging retention of small molecules pulmonary tissue. Hydrolysable ester conjugates PEG₁₀₀₀, PEG₂₀₀₀, ₂₀₀₀, PEG₃₄₀₀ prednisolone, model drug cleared from lungs within few minutes, were synthesised thoroughly characterised. The stable buffers with hydrolysis half-lives ranging 1h to 70 h, depending on pH...
The disposition of seven marketed and two AstraZeneca acid (organic anion) compounds with a range volume distribution at steady state (<i>V</i><sub>ss</sub>) clearance have been profiled in rat dog. Pharmacokinetic (PK) parameters along liver muscle tissue levels were collected, their contributions to total <i>V</i><sub>ss</sub> calculated. physiologically based prediction correlated (all predictions within 2-fold) the obtained from plasma PK analysis. drugs atypically high values could be...
A series of dibasic des-hydroxy β2 receptor agonists has been prepared and evaluated for potential as inhaled ultralong acting bronchodilators. Determination activities at the human β-adrenoreceptors demonstrated a highly potent selective that were progressed to further study in guinea pig histamine-induced bronchoconstriction model. Following assessment by onset studies tracheal rings bronchial contracted with methacholine (guinea pigs) or carbachol (humans), duration action pigs after...
A group of nine phenylynamines (PhC⋮CNH2, PhC⋮CNHCH(CH3)2, PhC⋮CNHC6H11, PhC⋮CNHC6H5, PhC⋮CNHC6F5, PhC⋮CN(CH2)5, PhC⋮CN(CH2CH2)2O, PhC⋮CN(CH2CH2CN)2, and PhC⋮CN(CH3)C6F5) were generated in aqueous solution by flash photolyic decarbonylation the corresponding phenylaminocyclopropenones, kinetics their facile decay that medium studied. This is catalyzed acids for all ynaminesprimary, secondary, tertiaryand also bases primary secondary ynamines. Solvent isotope effects form acid−base catalysis...
While cobalt is an essential micronutrient for vitamin B12 synthesis in the horse, at supraphysiological concentrations, it has been shown to enhance performance human subjects and rats, there evidence that its administration high doses horses poses a welfare threat. Animal sport regulators currently control abuse via international race day thresholds, but this work was initiated explore means of potentially adding application those thresholds since may be present physiological...
This comprehensive review describes contemporary computational (in silico) quantitative structure-activity relationship (QSAR) approaches that have been used to elucidate the molecular features influence Absorption, Distribution, Metabolism and Elimination (ADME) of drugs. Recent studies applied 2D 3D QSAR, pharmacophore nonlinear techniques (for example: recursive partitioning, neural networks support vector machines) model ADME processes. Furthermore, this highlights some challenges...
All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs) of new chemical entities (NCEs) and mathematical prediction helps select the best NCE candidate with regard adverse effects resulting from a DDI before any costly clinical studies. Most current models assume that liver is homogeneous organ where majority metabolism occurs. However, circulatory system has complex hierarchical geometry which distributes xenobiotics throughout organ. Nevertheless,...