Approaching complete inhibition of P-glycoprotein at the human blood–brain barrier: an (R)-[(11)C]verapamil PET study

As P-glycoprotein (Pgp) inhibition at the blood–brain barrier (BBB) after administration of a single dose of tariquidar is transient, we performed positron emission tomography (PET) scans with the Pgp substrate (R)-[(11)C]verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume (V(T)) of (R)-[(11)C]verapamil in whole-brain gray matter increased by 273±78% relative to baseline scans without tariquidar, which was higher than previously reported V(T) increases. During tariquidar infusion whole-brain V(T) was comparable to V(T) in the pituitary gland, a region not protected by the BBB, which suggested that we were approaching complete Pgp inhibition at the human BBB.