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Abstract #1533

Pharmacological MRI with Continuous ASL in Conscious Rats: Characterizing the Relationship Between CBF Response to CNS Compounds & Plasma Concentration Levels

Alexandre Coimbra1, Denise Welsh1, Diane Posavec1, Amy Vanko1, Richard Baumgartner2, Christopher Regan3, Andrew Danziger3, Matthew Baran3, Kristina Groover3, Jacquelynn Cook1, Joseph Lynch3, Jason Uslaner3, Donald Williams1

1Imaging, Merck & Co, Inc, West Point, PA, United States; 2Biometrics, Merck & Co, Inc, Rahway, NJ, United States; 3Central Pharm, Merck & Co, Inc, West Point, PA

Pharmacological functional MRI techniques have been used to assess drug effects in the central nervous system, however little has been done to characterize the relationship between the phMRI pharmacodynamic (PD) response and plasma concentration (pharmacokinetics, PK) of the compound being evaluated. This study aimed at exploring PK/PD relationships of phMRI response to two CNS acting compounds in conscious rats, donepezil and lorazepam using arterial spin labeling (ASL) measurements of CBF. Overall, these results provide insight into CBF PK/PD relationships and suggest potential use of conscious rat ASL as a platform providing translational biomarkers for CNS compound dose selection.