| Timetable |
| Download Conference Program |
| Download All Abstracts |
| Zoom Access |
| Corporate Program |
Poster Presentations
Day 3, June 24（Tue.）
Room P (Maesato East, Foyer, Ocean Wing)
- 3P-PM-06
Localized Transporter Inhibition and MSI: Advancing CNS Drug Penetration Studies
(Eisai Co., Ltd.)
oYoko Nagaya, Tomomi Ishida, Yoshitane Nozaki
Understanding drug penetration mechanism into the central nervous system (CNS) is essential for CNS drug discovery. While systemic administration of chemical inhibitors is employed to investigate the role of efflux transporters in drug brain penetration, their use is often limited by complex dosing conditions and systemic side effects. This study evaluated the usefulness of localized application of chemical inhibitors in combination with mass spectrometry imaging (MSI) to elucidate CNS drug penetration mechanisms while simplifying experimental conditions. Microdialysis probes were implanted bilaterally into rat brains, with one probe perfused with a P-gp/BCRP inhibitor and the other perfused with a control solution. Plasma and dialysate were collected under steady-state conditions during intravenous infusion of P-gp substrate drugs. Brain tissue sections (10 µm) were analyzed using targeted desorption electrospray ionization (DESI)-MSI. MSI confirmed the precise localization of inhibitors without diffusion beyond the probe implantation site. In the inhibitor-perfused region, dialysate drug concentrations increased 2 to 5-fold compared to controls, and MSI revealed a slight elevation in P-gp substrate intensity. This study demonstrates the effectiveness of localized transporter inhibition for investigating CNS drug penetration mechanism, offering a refined approach without systemic side effects or reliance on transgenic models.