Nasal Delivery of P-gp Substrates to the Brain through Nose-brain Pathway
News Mar 28, 2011
Well-known P-gp substrates, verapamil and talinolol, were perfused nasally or infused intravenously when plasma concentrations following intravenous infusion and nasal perfusion showed similar profiles. The concentration of verapamil in the brain after nasal perfusion was twice higher than that after intravenous infusion. Although talinolol in the brain and the CSF after i.v. infusion were below the detection limit, it was detected after nasal perfusion. When rats were treated with cyclosporin A, brain concentrations of verapamil after both administrations were increased significantly, while those of talinolol were not significantly changed. Since the permeability of talinolol is low, talinolol in the brain which was transported directly from the nasal cavity has little chance of transport by P-gp localized in the apical membrane of cerebral microvessel endothelial cells. The drug delivery potential utilizing the nose-CNS route was confirmed for P-gp substrates. The delivery of talinolol to the brain was more significant than verapamil, suggesting that nasal administration is more useful strategy for the brain delivery of low permeable P-gp substrates than the use of P-gp inhibitors.
This article is published online in the journal Drug, Metabolism and Pharmacokinetics and is free to access.
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