Amifostine (WR-2721, delivered as Ethyol) is a radioprotector agent that reduces
the likelihood of early and/or late biological effects by eliminating free radical particles
during ionizing radiation fraction (radiotherapy). It activates in under normal tissues
conditions to reduce mutation and fraction in DNA. Among 4000 prodrug compounds,
amifostine is the only agent has been approved from the US Food and Drug
Administration in clinical purposes. The main effective mechanisms of amifostine are
based on scavenging for free radical, improving for DNA repair step and indication of
cellular hypoxia. In the same time, this drug is not widely used around the world for
different reasons mainly its high cost and toxicity level (lethal dose). Conjugating a
monoclonal antibody with amifostine by a suitable linker is a process of Antibody Drug
Conjugate producing immuno-radioprotector molecule hypothesis. Administrated
molecule is an approach of targeted delivery therapy that increases the dosage uptake into
particular area of treatment to minimize the dose distribution in non-targeted area in the
body.
In the present work, we proposed a three-compartment system model to simulate
the two-pore theory pathway of an immuno-radioprotector molecule when it is crossing
the physiological barriers. The model investigated its distribution and elimination in
porous media (with both large and small pores) within a pharmacokinetics
compartmented model approach.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/32533 |
| Date | January 2015 |
| Creators | Alhassani, Maha |
| Contributors | Yagoub, Mustapha |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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