Fig. 8.

P-gp and Bcrp are critical determinants of BBB permeability to currently marketed statin drugs. 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 equal concentrations of radiolabeled statins (0.013 μM total concentration). Each experiment was conducted in the presence and absence of PSC833 (5 μM), FTC (10 μM), or GF120918 (10 μM) to limit the involvement of P-gp and/or Bcrp in the brain microvascular transport of statin drugs. 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).