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Open AccessChallenges in translational drug research in neuropathic and inflammatory pain: the prerequisites for a new paradigm
Despite an improved understanding of the molecular mechanisms of nociception, existing analgesic drugs remain limited in terms of efficacy in chronic conditions, such as neuropathic pain. Here, we explore the ...
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Article
Open AccessAssessment of Interspecies Differences in Drug-Induced QTc Interval Prolongation in Cynomolgus Monkeys, Dogs and Humans
The selection of the most suitable animal species and subsequent translation of the concentration-effect relationship to humans are critical steps for accurate assessment of the pro-arrhythmic risk of candidat...
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Article
Open AccessGenerating Virtual Patients by Multivariate and Discrete Re-Sampling Techniques
Clinical Trial Simulations (CTS) are a valuable tool for decision-making during drug development. However, to obtain realistic simulation scenarios, the patients included in the CTS must be representative of t...
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Article
Open AccessPrediction of Disease Progression, Treatment Response and Dropout in Chronic Obstructive Pulmonary Disease (COPD)
Drug development in chronic obstructive pulmonary disease (COPD) has been characterised by unacceptably high failure rates. In addition to the poor sensitivity in forced expiratory volume in one second (FEV1), nu...
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Article
Semi-mechanistic Modelling of the Analgesic Effect of Gabapentin in the Formalin-Induced Rat Model of Experimental Pain
The formalin-induced rat model of nociception involves moderate continuous pain. Formalin-induced pain results in a typical repetitive flinching behaviour, which displays a biphasic pattern characterised by pe...
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Article
Application of ED-optimality to screening experiments for analgesic compounds in an experimental model of neuropathic pain
In spite of the evidence regarding high variability in the response to evoked pain, little attention has been paid to its impact on the screening of drugs for inflammatory and neuropathic pain. In this study, ...
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Article
Optimised protocol design for the screening of analgesic compounds in neuropathic pain
We have previously shown how screening experiments for neuropathic pain can be optimised taking into account parameter and model uncertainty. Here we demonstrate how optimised protocols can be used to screen a...
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Article
298 Cd3+Cd4+-Lymphocytes as Biomarker Predicting the Outcome of Pediatric Haematopoietic Stem Cell Transplantation Recipients
Introduction: Haematopoietic stem cell transplantation (HSCT) may be complicated by severe infectious complications, graft-versus-host disease (GvHD) and relapse/graft failures depending on the lymphocyte immu...
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Article
Pharmacokinetics and pharmacodynamics of propofol 6% SAZN versus propofol 1% SAZN and Diprivan-10 for short-term sedation following coronary artery bypass surgery
Objective: A new formulation of propofol 6% in Lipofundin MCT/LCT 10% (propofol 6% SAZN) has been developed in order to reduce the fat, emulsifier and volume load that is given during pr...
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Article
Time course of action of three adenosine A1 receptor agonists with differing lipophilicity in rats: comparison of pharmacokinetic, haemodynamic and EEG effects
In this study we investigated the relationship between the pharmacokinetics and the cardiovascular and electroencephalogram (EEG) effects of three adenosine agonists with differing lipophilicity. Conscious nor...
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Population analysis of the non-linear red blood cell partitioning of draflazine following various infusion durations
Objective: The pharmacokinetics and non-linear red blood cell partitioning of the nucleoside transport inhibitor draflazine were investigated in 19 healthy male and female subjects (age ...
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Article
The Impact of Arteriovenous Concentration Differences on Pharmacodynamic Parameter Estimates
In many pharmacodynamic investigations venous drug concentrations are measured and linked to effect-site concentrations by means of a traditional first-order effect-compartment model to estimate pharmacodynami.....
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Article
The Use of Intracerebral Microdialysis for the Determination of Pharmacokinetic Profiles of Anticancer Drugs in Tumor-Bearing Rat Brain
Purpose. The use of intracerebral microdialysis as a tool to measure the penetration of anticancer agents in brain tumor was investigated.
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Abstracts of papers and posters Pharmacological Meeting
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Abstracts of papers and posters Meeting on Pharmaceutical Sciences
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Abstracts of papers Pharmacological Meeting
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Pharmacokinetic-pharmacodynamic modelling in pre-clinical investigations: principles and perspectives
A new approach to preclinical pharmacodynamic investigations is presented which allows, in addition to information on the nature of the pharmacological properties of new chemical entities, also important quant...
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Article
Drug transport across the blood-brain barrier
This is the third part of a review on the transport of drugs across the blood-brain barrier. In the first two parts, the anatomical and physiological aspects and the various techniques that can be used to stud...
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Drug transport across the blood — brain barrier
This is part II of a review on the transport of drugs across the blood-brain barrier. In this part, the emphasis is on the various experimental techniques that can be used to characterize the blood — brain bar...
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Article
Influence of single- and multiple-dose omeprazole treatment on nifedipine pharmacokinetics and effects in healthy subjects
The effects of single dose (20 mg) and short-term (20 mg/day for 8 days) oral treatment with omeprazole on the pharmacokinetics and effects of oral nifedipine (10 mg capsule) and on gastric pH have been invest...