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  • Meeting abstract
  • Open Access

Decreased blood-brain barrier P-glycoprotein function with aging

  • 1,
  • 2,
  • 1, 3,
  • 1,
  • 4,
  • 1 and
  • 1, 3Email author
BMC Pharmacology20088 (Suppl 1) :A48

  • Published:


  • Positron Emission Tomography
  • Verapamil
  • Distribution Volume
  • Aged Group
  • Positron Emission Tomography Scan


P-glycoprotein (P-gp) acts at the blood-brain barrier (BBB) as an active cell membrane efflux pump for several endogenous and exogenous compounds. The P-gp substrate (R)-[11C]verapamil (VPM) can be used to measure P-gp-mediated transport at the BBB in vivo with positron emission tomography (PET). The distribution volume (DV) of VPM has been shown to inversely reflect P-gp function in the BBB [1].

Materials and methods

A young (n = 7, mean age: 28.0 ± 3.8 years) and an aged group (n = 6, mean age: 69.4 ± 8.5 years) of healthy volunteers underwent dynamic VPM PET scans and arterial blood sampling. Radiolabelled metabolites of VPM were quantified by a previously described combined solid-phase extraction/HPLC protocol [1]. A whole-brain grey matter region was defined by using the Hammersmith n20r49 brain atlas [2]. The DV of VPM was estimated by using a 2-rate-constant-1-tissue-compartment model [1].


Mean DV s (± standard deviation) of VPM were 0.50 ± 0.08 for the young and 0.63 ± 0.13 for the aged group (+27% for the aged group, p = 0.04, 2-tailed t-test). There was no significant difference in VPM metabolism between the young and the aged group (area under the curve of the fraction of polar [11C]metabolites of VPM versus time in arterial plasma: 12.7 ± 2.4 and 14.1 ± 3.6 for the young and the aged group, respectively, p = 0.19, 2-tailed t-test).


Our data confirm previous results that older subjects show significantly decreased P-gp function in the BBB [1, 3]. Decreased P-gp function can lead to increased accumulation of toxins and drugs in the aging brain and could thus be a risk factor for the development of neurodegenerative disease.

Authors’ Affiliations

Department of Clinical Pharmacology, Medical University of Vienna, 1090, Vienna, Austria
Department of Medical Computer Sciences, Medical University of Vienna, 1090, Vienna, Austria
Department of Radiopharmaceuticals, Austrian Research Centers GmbH – ARC, 2444, Seibersdorf, Austria
Department of Nuclear Medicine, Medical University of Vienna, 1090, Vienna, Austria


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© Bauer et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.