METHOD DEVELOPMENT FOR INVESTIGATION THE BLOOD-BRAIN BARRIER PERMEABILITY WITH INTRANASALLY ADMINISTRATED P-GP SUBSTRATE
AIM: Intranasal administration of substances is known to be a promising form of drug delivery for decades now. The nasal cavity provides many routes into the brain through the blood and also directly into the central nervous system (CNS) through the olfactory and trigeminal nerves. We wanted to develop a method for investigation the P-gp function at the blood-brain barrier (BBB) using intranasally administered P-gp substrate, quinidine (QND).METHODS: Dual-probe in vivo microdialysis was used to monitor the blood and brain levels of the drug in anesthetized rats. Control measurements were made with only intranasal QND treatment. Then the results were compared with intranasal QND administration after intranasal/intravenous P-gp inhibitor, valspodar (PSC-833) treatment and with different dosages of intranasal vasoconstrictor, epinephrine (ADR) co-administration. RESULTS: The result of intranasal PSC pretreatment and low dose intranasal ADR co-administration showed infinitesimal difference compared to control, but intravenous PSC treatment significantly increased QND concentration in the brain as well as high dosage ADR co-administration. CONCLUSON: The method seems to be useful for testing P-gp interactions and BBB permeability. The P-gp substrate concentration in the CNS can be increased with ADR co-administration and with intravenous P-gp inhibitor pretreatment.