A number of the studies on pharmacokinetics of fluorinated
pyrimidines have been precisely reported. In mice bearing Ehrlich
ascites carcinoma,
5-FU showed highest concentration in the lung and kidney immediately after i.v. administration of
5-FU, and in the liver, it showed rather lower concentration but for a longer period.
5-FU in blood was transferred into
ascites fluid rapidly, and thus, the level of
5-FU in
ascites fluid became higher than that in blood. FT is a masked compound of
5-FU, having a tetrahydrofuryl group.
Drug metabolizing
enzyme, natural degradation, and
thymidine phosphorylase are considered to be responsible for the molecular conversion of FT into
5-FU. In order to increase the level of
drug metabolizing
enzyme, P450 in the liver of
tumor bearers, of which P450 level was extremely lower as compared to normal individuals,
phenobarbital was very effective from our previous experiment. Clinically,
phenobarbital 200mg/day for 3 successive days was administered in prior to FT, and a better response was obtained than FT alone. Prevention from degradation of
5-FU in the liver by
uracil kept higher level of
5-FU in blood.
HCFU and 5'DFUR are also masked form of
5-FU and are converted to
5-FU in the liver.