Abstract:
:Receptor occupancy (RO) PET is a non-invasive way to determine drug on target. Given the complexity of procedures, long acquisition times, and high cost, ligand displacement imaging trials often have a limited size and produce sparse RO results over the time course of the blocking drug. To take the best advantage of the available data, we propose a Bayesian hierarchical model to analyze RO as a function of the displacing drug. The model has three components: the first estimates RO using brain regional time-radioactivity concentrations, the second shapes the pharmacokinetic profile of the blocking drug, and the last relates PK to RO. Compared to standard 2-steps RO estimation methods, our Bayesian approach quantifies the variability of the individual RO measures. The model has also useful prediction capabilities: to quantify brain RO for dosage regimens of the drug that were not tested in the experiment. This permits the optimal dose selection of neuroscience drugs at a limited cost. We illustrate the method in the prediction of RO after multiple dosing from a single-dose trial.
journal_name
J Biopharm Statjournal_title
Journal of biopharmaceutical statisticsauthors
Vandenhende F,Renard D,Nie Y,Kumar A,Miller J,Tauscher J,Witcher J,Zhou Y,Wong DFdoi
10.1080/10543400701697158subject
Has Abstractpub_date
2008-01-01 00:00:00pages
256-72issue
2eissn
1054-3406issn
1520-5711pii
791344142journal_volume
18pub_type
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