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|Title: ||Bayesian hierarchical modeling of receptor occupancy in PET trials|
|Authors: ||Vandenhende, F.|
Wong, D. F.
|Issue Date: ||2008|
|Publisher: ||TAYLOR & FRANCIS INC|
|Citation: ||JOURNAL OF BIOPHARMACEUTICAL STATISTICS, 18(2). p. 256-272|
|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.|
|Notes: ||[Vandenhende, F.; Renard, D.] Lilly Res Labs, Mont St Guibert, Belgium. [Nie, Y.] Univ Hassrlt, Biostat Dept, Diepenbeek, Belgium. [Kumar, A.; Zhou, Y.] PET Ctr, Sch Med, Baltimore, MD USA. [Miller, J.] Lilly Res Labs, Clin Pharmacol, Indianapolis, IN USA. [Tauscher, J.] Lilly Res Labs, Dept Imaging, Indianapolis, IN USA. [Witcher, J.] Lilly Res Labs, Global PK PD, Indianapolis, IN USA.|
|ISI #: ||000253763000004|
|Type: ||Journal Contribution|
|Validation: ||ecoom, 2009|
|Appears in Collections: ||Research publications|
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