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Clin Pharmacol Ther. 2006 Jun;79(6):540-8.

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

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  • 1Department of Clinical Pharmacology and Pharmacy, VU University Medical Centre, Amsterdam, The Netherlands. R.Toornvliet@vumc.nl

Abstract

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)-[(11)C]verapamil and positron emission tomography were used to assess gray matter P-gp function. Because (R)-[(11)C]verapamil is a substrate for P-gp, the volume of distribution of (R)-[(11)C]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.

PMID:
16765142
[PubMed - indexed for MEDLINE]
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