The effect of structural modifications of 5-fluorouracil derivatives on their transport and biodegradation by isolated rat jejunum.

The continuous-perfusion technique was used in an isolated segment of everted rat jejunum to study transport and biotransformation processes in a series of cancerostatic derivatives of 5-fluorouracil. Metabolic alterations during penetration of the intestinal wall were assessed by high-performance liquid chromatography (HPLC). Octanol-buffer partition coefficients were measured, and the lipophilicity of the study compounds and fragmental constants for their sugar moieties were assessed. In the present series of 5-fluorouracil derivatives, there was no correlation between lipophilicity and metabolic cleavage to 5-fluorouracil, but a correlation was found between lipophilicity and the transport rate. Remarkable stability of the nucleoside bond and high biotransport were observed with 5'-chloro-5-fluorouridine, suggesting a different mode of activation for this derivative.