Graduation Date

Spring 5-4-2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Pharmaceutical Sciences

First Advisor

Dr. Daryl J Murry, PharmD

Abstract

Group 3 medulloblastoma (MB) has the worst prognosis of the MB subgroups associated with elevated MYC expression and a 5-year survival rate of

Quantitation of EPZ was performed on a Shimadzu LC-MS/MS system utilizing electrospray ionization operated in positive mode. The validated assay was linear from 0.2 to 500 ng/mL. Metabolic stability studies demonstrated slow intrinsic clearance of EPZ in mouse and human liver microsomes, suggesting no CYP-mediated metabolism. Additionally, EPZ exhibited low binding affinity to plasma and brain proteins and high apparent permeability across artificial membranes, indicating efficient membrane penetration. Drug transporter studies identified EPZ as a substrate of OATP1B1.

In an in-vivo pharmacokinetic study, healthy male BALB/c mice received a single oral EPZ dose of 100 mg/kg. The maximum plasma concentration (Cmax) was 10154.31 ± 2450.74, and clearance was 12.41 ± 4.17. Furthermore, EPZ achieved brain concentrations of 874.23 ± 412.71 ng/g. These findings collectively suggest EPZ’s potential suitability for oral administration and ability to cross the BBB.

Comments

2024 Copyright, the authors

Rights

The author holds the copyright to this work and any reuse or permissions must be obtained from the author directly.

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