Final answer:
Amino acid ester prodrugs of floxuridine aim to enhance oral bioavailability and minimize toxicity by influencing the rate of hydrolysis through structure, stereochemistry, and esterification site, with enzymatic stability and permeability across Caco-2 monolayers being key factors.
Step-by-step explanation:
Floxuridine Prodrugs and Enhanced Therapeutic Efficacy
Floxuridine prodrugs, modified with amino acid esters, have been researched to increase oral bioavailability and reduce toxicity by protection against the rapid conversion to 5-Fluorouracil (5-FU) in the body. The studies, such as those by Vig et al. (2003), show that the structure, stereochemistry, and site of esterification significantly influence the rate of hydrolysis. This control over hydrolysis rates is crucial because it affects floxuridine's disposition and therapeutic effect. For example, compared to other amino acid esters, isoleucyl ester prodrugs demonstrate greater enzymatic stability, suggesting potential as promising candidates for prodrug modification. Additionally, enzymatic bioconversion is predominant over non-enzymatic in intestinal absorption, and the permeability of prodrugs across Caco-2 monolayers is crucial in determining their suitability for oral administration.