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In vivo dose finding of tariquidar using (R)-[11C]verapamil μPET

  • Oliver Langer1, 2Email author,
  • Jens Bankstahl1,
  • Claudia Kuntner1,
  • Aiman Abrahim1, 2,
  • Rudolf Karch3,
  • Johann Stanek1,
  • Thomas Wanek1,
  • Maria Zsebedics1,
  • Kurt Kletter4,
  • Wolfgang Löscher5,
  • Markus Müller2 and
  • Herbert Kvaternik1
BMC Pharmacology20077(Suppl 2):A22

Published: 14 November 2007


Confidence IntervalPositron Emission TomographyPotential ApplicationVerapamilEffective Dose


Tariquidar (TQD, Xenova, UK) is a third-generation inhibitor of the multidrug efflux transporter P-glycoprotein (P-gp) with potential applications in neurology and oncology in order to increase drug exposure of tissues targeted for treatment. We used small-animal positron emission tomography (μPET) with the P-gp substrate (R)-[11C]verapamil (VPM) in order to measure in vivo the degree of P-gp inhibition at the rat blood-brain barrier (BBB) after administration of different doses of TQD.


Wistar Unilever rats received intravenous doses of 0, 1, 3, 5, 7.5 and 15 mg/kg of TQD followed by a 1-hour VPM μPET scan recorded at 2 hours after TQD administration. Brain-to-plasma radioactivity ratios were fitted to a sigmoidal dose-response curve.


TQD inhibited P-gp-mediated efflux of VPM across the BBB with an apparent half-maximum effective dose (ED50) of 6.6 mg/kg (95% confidence interval: 4.9–8.2 mg/kg) which was in good agreement with previous data reported in mice for another P-gp substrate (loperamide, ED50: 5.7 mg/kg) [1]. Brain-to-plasma radioactivity ratios after 0 and 15 mg/kg of TQD were 0.23 and 3.15, respectively.


Our data suggest that TQD is a potent inhibitor of P-gp at the rat BBB. Moreover, VPM PET appears to be a useful tool for in vivo dose finding of novel P-gp inhibitors in animals and humans.

Authors’ Affiliations

Department of Radiopharmaceuticals, ARCGmbH, Seibersdorf, Austria
Department of Clinical Pharmacology, Medical University of Vienna, Austria
Department of Medical Computer Sciences, Medical University of Vienna, Austria
Department of Nuclear Medicine, Medical University of Vienna, Austria
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine Hannover, Germany


  1. Choo EF, Kurnik D, Muszkat M, Ohkubo T, Shay SD, Higginbotham JN, Glaeser H, Kim RB, Wood AJ, Wilkinson GR: Differential in vivo sensitivity to inhibition of P-glycoprotein located in lymphocytes, testes, and the blood-brain barrier. J Pharmacol Exp Ther. 2006, 317: 1012-1018. 10.1124/jpet.105.099648.View ArticlePubMedGoogle Scholar


© Langer et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd.