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Type: Journal article
Title: Pharmacodynamic modelling of placebo and buprenorphine effects on event-related potentials in experimental pain
Author: Juul, R.
Foster, D.
Upton, R.
Andresen, T.
Graversen, C.
Drewes, A.
Christrup, L.
Kreilgaard, M.
Citation: Basic and Clinical Pharmacology and Toxicology, 2014; 115(4):343-351
Publisher: Wiley
Issue Date: 2014
ISSN: 1742-7835
Statement of
R.V. Juul, D.J.R. Foster, R.N. Upton, T. Andresen, C. Graversen, A.M. Drewes, L.L. Christrup and M. Kreilgaard
Abstract: The purpose of the study was to investigate placebo and buprenorphine effects on event-related potentials (ERPs) in experimental pain and the potential benefit of population pharmacodynamic modelling in data analysis. Nineteen healthy volun- teers received transdermal placebo and buprenorphine in a cross-over study. Drug plasma concentrations and ERPs after electrical stimulation at the median nerve with intensity adjusted to pain detection threshold were recorded until 144 hrs after administra- tion. Placebo and concentration-effect models were fitted to data using non-linear mixed-effects modelling implemented in NON- MEM (V7.2.0.). Pharmacodynamic models were developed to adequately describe both placebo and buprenorphine ERP data. Models predicted significant placebo effects, but did not predict significant effects related to buprenorphine concentration. Mod- els revealed that ERPs varied both between subjects and between study occasions. ERPs were found to be reproducible within subjects and occasions as population variance was found to be eight times higher than the unexplained variances. Between-sub- ject variance accounted for more than 75% of the population variance. In conclusion, pharmacodynamic modelling was success- fully implemented to allow for placebo and variability correction in ERP of experimental pain. Improved outcome of ERP studies can be expected if variation between subjects and
Keywords: Humans
Administration, Cutaneous
Cross-Over Studies
Pain Threshold
Evoked Potentials
Models, Theoretical
Healthy Volunteers
Rights: © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)
DOI: 10.1111/bcpt.12217
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