Lymphatic and plasma transport of 1-(2-tetrahydrofuryl)-5-fluorouracil by polyacrylic acid aqueous gel after rectal administration and its antitumor effect on Yoshida sarcoma implanted in rats

Abstract

The inhibition of tumor growth estimated by the size and the weight of the implanted Yoshida sarcoma was investigated in the rat after the administration of suppositories containing 1-(2-tetrahydrofury1)-5-fluorouracil (FT-207) alone or in combination with adjuvants. The inhibitory effect on the tumor growth was shown to be stronger by rectal administration of FT-207 as a polyacrylic acid aqueous gel suppository containing additive (uracil) than by a Witepsol suppository. FT-207 concentrations in both plasma and the tumor tissue after a single rectal administration on the 10th day after the tumor implantation were higher from the aqueous gel suppository than the Witepsol suppository, and were further increased by the addition of oleic acid into the aqueous gel suppository. While the plasma concentration of FT-207 following repeated administration was almost the same as those after the single administration, the tumor concentration of drug tended to increase with repeated administration, especially in the case of polyacrylic acid aqueous gel suppositories with or without uracil. It can be considered from the result of the present study that the increase in the inhibitory effect on the tumor growth by the coadministration of additive (uracil) with FT-207 are due to the inhibition of 5-fluorouracil degradation by uracil rather than the increased absorption of FT-207 by the adjuvant.