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

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