Introduction
Inhibition of the multidrug efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier (BBB) is considered a promising strategy in order to increase intracerebral penetration of therapeutics, such as antiepileptic and anticancer drugs. The aim of this study was to evaluate the usefulness of (R)-[11C]verapamil (VPM) and small-animal positron emission tomography (μPET) to measure P-gp inhibition at the BBB following administration of the third-generation P-gp inhibitor tariquidar (TQD, Xenova, UK).
Methods
Five Wistar Unilever rats underwent paired VPM μPET scans, one baseline scan followed by i.v. administration of TQD (15 mg/kg) and a second PET scan at 2 hour after TQD administration. Arterial blood sampling was performed along with analysis of metabolism and plasma protein binding of VPM.
Results
Following TQD administration, the brain-to-plasma ratio of radioactivity was increased by a factor of 11–16 as compared to baseline scans, whereas VPM metabolism and plasma protein binding were left unaffected.
Conclusion
Our pilot data suggest that VPM PET is a sensitive tool to quantitatively visualize P-gp inhibition at the animal and human BBB.
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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Kuntner, C., Bankstahl, J., Abrahim, A. et al. P-Glycoprotein inhibition at the blood-brain barrier visualized with (R)-[11C]verapamil μPET. BMC Pharmacol 7 (Suppl 2), A24 (2007). https://doi.org/10.1186/1471-2210-7-S2-A24
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DOI: https://doi.org/10.1186/1471-2210-7-S2-A24