Pgp-mediated interaction between (R)-[11C]verapamil and tariquidar at the human blood-brain barrier: a comparison with rat data

Clin Pharmacol Ther. 2012 Feb;91(2):227-33. doi: 10.1038/clpt.2011.217. Epub 2011 Dec 14.


Using positron emission tomography (PET) imaging we assessed, in vivo, the interaction between a microdose of (R)-[(11)C]verapamil (a P-glycoprotein (Pgp) substrate) and escalating doses of the Pgp inhibitor tariquidar (3, 4, 6, and 8 mg/kg) at the blood-brain barrier (BBB) in healthy human subjects. We compared the dose-response relationship of tariquidar in humans with data obtained in rats using a similar methodology. Tariquidar was equipotent in humans and rats in its effect of increasing (R)-[(11)C]verapamil brain uptake (expressed as whole-brain volume of distribution (V(T))), with very similar half-maximum-effect concentrations. Both in humans and in rats, brain V(T) approached plateau levels at plasma tariquidar concentrations >1,000 ng/ml. However, Pgp inhibition in humans led to only a 2.7-fold increase in brain V(T) relative to baseline scans (before administration of tariquidar) as compared with 11.0-fold in rats. The results of this translational study add to the accumulating evidence that there are marked species-dependent differences in Pgp expression and functionality at the BBB.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • Animals
  • Blood-Brain Barrier / diagnostic imaging
  • Blood-Brain Barrier / drug effects*
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Carbon Radioisotopes
  • Dose-Response Relationship, Drug
  • Humans
  • Positron-Emission Tomography / methods
  • Positron-Emission Tomography / statistics & numerical data
  • Quinolines / blood
  • Quinolines / pharmacology*
  • Rats
  • Species Specificity
  • Verapamil / pharmacokinetics*


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Calcium Channel Blockers
  • Carbon Radioisotopes
  • Quinolines
  • Verapamil
  • tariquidar