Theoretical and Natural Science
- The Open Access Proceedings Series for Conferences
Theoretical and Natural Science
Vol. 29, 16 January 2024
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Improving brain penetration using elacridar—a P-glycoprotein and BCRP inhibitor
* Author to whom correspondence should be addressed.
Abstract
The central nervous system (CNS) is a site for a myriad of disorders and diseases, such as schizophrenia, Alzheimer’s disease, and Parkinson’s disease. Many medications targeting these illnesses remain challenged due to efflux transporters forming a blood-brain barrier (BBB). To combat such challenges, elacridar shown promise at inhibiting such transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), therefore improving brain penetration. However, as an early clinical candidate, many remain unknown about elacridar’s pharmacokinetic (PK) properties in the human body. This paper aims to obtain a better understanding of elacridar’s pharmacokinetic profile and predict the optimal dose and dose interval for its application in the clinic. To begin with, a series of basic PK models were created using fundamental PK equations and the models were fit to elacridar clinical data to obtain elacridar-specific PK parameters. Next, elacridar preclinical PK as well as in vitro inhibition assay were used to determine the therapeutic window. Our final, multiple-dose extravascular PK model reveals that the most convenient and effective dose regimen is 900 mg BID (bis in die; twice per day). With this elacridar PK model, researchers can leverage elacridar human PK to improve clinical outcomes.
Keywords
Blood-Brain Barrier, Pharmacokinetics Modeling, Elacridar, Efflux Transporters
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Data Availability
The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.
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- Volume Title
- Proceedings of the 2nd International Conference on Modern Medicine and Global Health
- ISBN (Print)
- 978-1-83558-279-4
- ISBN (Online)
- 978-1-83558-280-0
- Published Date
- 16 January 2024
- Series
- Theoretical and Natural Science
- ISSN (Print)
- 2753-8818
- ISSN (Online)
- 2753-8826
- DOI
- 10.54254/2753-8818/29/20240729
- Copyright
- 16 January 2024
- Open Access
- This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited