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

摘要

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)-[C-11] verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume (V-T) of (R)-[C-11] 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.