Effect of age on functional P-glycoprotein in the blood-brain barrier measured by use of (R)-[11C]verapamil and positron emission tomography

Rolf Toornvliet, Bart N.M. van Berckel, Gert Luurtsema, Mark Lubberink, Albert A. Geldof, Tessa M. Bosch, Ruud Oerlemans, Adriaan A. Lammertsma, Eric J.F. Franssen

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Introduction: P-glycoprotein (P-gp) is an efflux transporter responsible for the transport of various drugs across the blood-brain barrier (BBB). Loss of P-gp function with age may be one factor in the development and progression of neurodegenerative diseases. The aim of this study was to assess the effect of aging on BBB P-gp function. Furthermore, the relationship between BBB P-gp activity and peripheral P-gp activity in CD3-positive leukocytes was investigated. Finally, plasma pharmacokinetics of carbon 11-labeled (R)-verapamil was evaluated. Methods: (R)-[11C]verapamil and positron emission tomography were used to assess gray matter P-gp function. Because (R)-[11C]verapamil is a substrate for P-gp, the volume of distribution of (R)-[11C]verapamil in the brain inversely reflects P-gp function in the BBB. Results: Mean volume of distribution values for 5 young healthy volunteers (age range, 21-27 years) and 5 elderly healthy volunteers (age range, 59-68 years) were 0.62 ± 0.10 and 0.73 ± 0.07, respectively (P = .03). The activity index of P-gp activity in CD3-positive leukocytes was 2.88 ± 0.77 in young volunteers and 1.76 ± 0.58 in elderly volunteers (P = .02). Conclusion: This study showed decreased P-gp activity during aging. Consequently, the brain may be exposed to higher drug and toxin levels in elderly subjects.

Original languageEnglish
Pages (from-to)540-548
Number of pages9
JournalClinical Pharmacology and Therapeutics
Issue number6
Publication statusPublished - 1 Jun 2006

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