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• W2114446443 abstract "In vivo characterization of the brain pharmacokinetics of novel compounds provides important information for drug development decisions involving dose selection and the determination of administration regimes. In this context, the compound-target affinity is the key parameter to be estimated. However, if compounds exhibit a dynamic lag between plasma and target bound concentrations leading to pharmacological hysteresis, care needs to be taken to ensure the appropriate modeling approach is used so that the system is characterized correctly and that the resultant estimates of affinity are correct. This work focuses on characterizing different pharmacokinetic models that relate the plasma concentration to positron emission tomography outcomes measurements (e.g., volume of distribution and target occupancy) and their performance in estimating the true in vivo affinity. Measured (histamine H3 receptor antagonist—GSK189254) and simulated data sets enabled the investigation of different modeling approaches. An indirect pharmacokinetic-receptor occupancy model was identified as a suitable model for the calculation of affinity when a compound exhibits pharmacological hysteresis." @default.
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• W2114446443 date "2013-02-06" @default.
• W2114446443 modified "2023-09-22" @default.
• W2114446443 title "Kinetic Analysis of Drug–Target Interactions with PET for Characterization of Pharmacological Hysteresis" @default.
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• W2114446443 doi "https://doi.org/10.1038/jcbfm.2012.208" @default.
• W2114446443 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3652698" @default.
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