Figure 2.

Preclinical positron emission tomography (PET)-based drug–drug interaction study between the P-glycoprotein (Pgp) substrate (R)-[¹¹C]verapamil and the Pgp inhibitor tariquidar using Friend virus B-type (FVB) wild-type and transporter knockout mice. Shown are coronal (R)-[¹¹C]verapamil PET summation images (0–60 min) for paired scans acquired before (upper row) and after (lower row) i.v. pretreatment with tariquidar (15 mg/kg, 2 h before start of second PET scan). Radiation scale is expressed as a standardized uptake value. In PET scans before tariquidar pretreatment, brain uptake of (R)-[¹¹C]verapamil was low in animals expressing Pgp (wild-type and Bcrp1^−/−) and high in animals lacking Pgp (Mdr1a/b^−/− and Mdr1a/b^−/−Bcrp1^−/−). Following Pgp inhibition with tariquidar, brain uptake of (R)-[¹¹C]verapamil was within a comparable range in all four mouse types. Taken together, these data demonstrate that (R)-[¹¹C]verapamil is transported by Pgp at the mouse blood–brain barrier and not by breast cancer resistance protein.