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

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)-[C-11]verapamil and positron emission tomography were used to assess gray matter P-gp function. Because (R)-[C-11]verapamil is a substrate for P-gp, the volume of distribution of (R)-[C-11]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 C133-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.