Fig. 11.

P-gp and Bcrp have a similar effect on statin disposition in cerebral cortex, hippocampus, and cerebellum. Brain uptake of [³H]atorvastatin (A), [³H]pravastatin (B), and [³H]rosuvastatin (C) were measured by the in situ brain perfusion approach. Animals were treated with BMP-9 (1 μg/kg, i.p.; 6-hour treatment) in the presence and absence of LDN193189 (10 mg/kg, i.p.; 1-hour pretreatment) and perfused with a radiolabeled statin (0.013 μM total concentration). Each experiment was conducted in the presence and absence of GF120918 (10 μM) to determine involvement of the critical BBB efflux transporters P-gp and Bcrp in the brain microvascular transport of statin drugs. At the conclusion of this experiment, drug concentrations were measured in cerebral cortex, hippocampus, and cerebellum to evaluate brain regional differences in statin transport. Results are expressed as mean ± S.D. of six animals per time point. Asterisks represent data points that were significantly different from control animals (*p < 0.05; **p < 0.01).