The tissue:plasma (P t:p ) partition coefficients (PCs) are important drugspecific input parameters in physiologically based pharmacokinetic (PBPK) models used to estimate the disposition of drugs in biota. Until now the use of PBPK models in early stages of the drug discovery process was not possib
Determination of drug-induced changes in functional MRI signal using a pharmacokinetic model
โ Scribed by Alan S. Bloom; Raymond G. Hoffmann; Scott A. Fuller; John Pankiewicz; Harold H. Harsch; Elliot A. Stein
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 218 KB
- Volume
- 8
- Category
- Article
- ISSN
- 1065-9471
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โฆ Synopsis
As the applications of functional magnetic resonance imaging (fMRI) expand, there is a need for the development of new strategies for data extraction and analysis that do not require the presentation of stimuli in a repeated on/off pattern. A description and evaluation of a method and computer algorithm for the detection and analysis of brain activation patterns following acute drug administration using fMRI are presented. A waveform analysis protocol (WAP) input function has been developed that is based upon the single-dose pharmacokinetics of a drug of interest. As a result of this analysis, regional brain activation can be characterized by its localization and intensity of activation, onset of action, time to peak effect, and duration of action. A global statistical test for significant drug effects based upon the probability of a voxel being activated by a saline vehicle injection is applied to grouped data on a voxel by voxel basis. Representative data are presented using nicotine as a prototypical agent. Using this method, statistically significant drug-induced brain activation has been identified in several key cortical and subcortical brain regions.
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