No abstract

1 Homozygously mdr1a gene disrupted mice (mdr1a(7/7) mice) and wild type mice (mdr1a(+/+) mice) were used to develop a method for P-glycoprotein (P-gp) function imaging non-invasively and to study the eect of a P-gp reversal agent on its function in vivo. ]verapamil accumulation in the brain of mdr1a(+/+) mice was increased by cyclosporin A to levels comparable with those in mdr1a(7/7) mice, indicating that reversal of P-gp mediated eux can be monitored by PET. 5 We conclude that cyclosporin A can fully block the P-gp function in the blood brain barrier and the testes and that PET enables the in vivo measurement of P-gp function and reversal of its function noninvasively.

This study showed decreased P-gp activity during aging. Consequently, the brain may be exposed to higher drug and toxin levels in elderly subjects.