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.
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.
Authors: M Bauer; M Zeitlinger; R Karch; P Matzneller; J Stanek; W Jäger; M Böhmdorfer; W Wadsak; M Mitterhauser; J P Bankstahl; W Löscher; M Koepp; C Kuntner; M Müller; Oliver Langer Journal: Clin Pharmacol Ther Date: 2011-12-14 Impact factor: 6.875
Authors: Jurgen E M Mourik; Mark Lubberink; Alie Schuitemaker; Nelleke Tolboom; Bart N M van Berckel; Adriaan A Lammertsma; Ronald Boellaard Journal: Eur J Nucl Med Mol Imaging Date: 2008-11-22 Impact factor: 9.236
Authors: Viktoria Zoufal; Thomas Wanek; Markus Krohn; Severin Mairinger; Thomas Filip; Michael Sauberer; Johann Stanek; Thomas Pekar; Martin Bauer; Jens Pahnke; Oliver Langer Journal: J Cereb Blood Flow Metab Date: 2018-10-24 Impact factor: 6.200