ORCID ID
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.
Recommended Citation
Kshirsagar, Pratiksha U., "Assessment of In-Vitro and In-Vivo Pre-Clinical Pharmacokinetics of EPZ015666; A Novel Small molecule for medulloblastoma treatment" (2024). Theses & Dissertations. 824.
https://digitalcommons.unmc.edu/etd/824
Included in
Oncology Commons, Other Pharmacy and Pharmaceutical Sciences Commons, Pediatrics Commons, Pharmaceutics and Drug Design Commons, Pharmacology Commons, Translational Medical Research Commons
Comments
2024 Copyright, the authors