Postdoctoral Candidate State University of New York at Buffalo Buffalo, New York
Presentation Description: Sucrose is a widely used BBB permeability marker, similar to a low molecular weight drug having low passive permeability. Typically brain uptake measurements done through single time point analysis or multiple time point analysis do not consider efflux processes. Therefore, in this study we compared brain uptake measurements using single time point, multiple time point and a 3-compartment model after an IV bolus injection of [13C12] sucrose in C57/BL6J mice. The 3-compartment model fit the data well and the value for brain uptake clearance and efflux was found to correlate well with literature values. In contrast, Kin estimates from both single time point evaluation and Patlak analysis were underestimated with increasing experimental time, indicating dependence on experimental duration. Our study shows brain uptake measurements of low permeable substances might be significantly underestimated using non-compartmental brain uptake measurements due to the influence of bulk flow mediated efflux.
Understanding the process of bulk flow mediated efflux
Understanding different non-compartmental means of calculating brain uptake clearance values (Kin)
Understanding the impact of bulk flow mediated efflux in unwanted underestimations of Kin measurements when using non-compartmental estimation methods when compared with a 3 compartment model