Author(s): Wang Q, Yang H, Miller DW, Elmquist WF
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Abstract The p-glycoprotein is a transmembrane efflux transporter found on the luminal side of the capillary endothelial cells that comprise the blood-brain barrier. This study examined the effect of a p-glycoprotein inhibitor, cyclosporin A, on the distribution to the brain of a p-glycoprotein substrate, rhodamine-123, in freely moving rats using intracerebral microdialysis coupled with on-line HPLC analysis. Results from crossover experiments show that the coadministration of cyclosporin A significantly increased the distribution of rhodamine-123 to the brain. The plasma disposition of rhodamine-123 was unchanged by cyclosporin A, indicating that the change in brain exposure was mediated by a process at the level of the blood-brain barrier, possibly by inhibition of the p-glycoprotein efflux transporter. This finding suggests a functional activity of the p-glycoprotein in the blood-brain barrier and validates an in vivo model to examine the role of this transporter in the brain distribution of drugs.
This article was published in Biochem Biophys Res Commun
and referenced in Journal of Bioequivalence & Bioavailability