1-Hexylcarbamoyl-5-fluorouracil(HCFU)の経口及び直腸吸収に及ぼすジメチルβ-シクロデキストリンの影響
1988 年 108 巻 2 号 p. 156-163
詳細
1988 年 108 巻 2 号 p. 156-163
Inclusion complexes of anticancer drug 1-hexylcarbamoyl-5-fluorouracil(HCFU) with β-cyclodextrin(β-CyD), heptakis(2, 6-di-O-methyl)-β-CyD(DM-β-CyD) and heptakis (2, 3, 6-tri-O-methyl)-β-CyD(TM-β-CyD) in the molar ratio of 1 : 1 were prepared, and their dissolution, release from a suppository base and oral or rectal absorption behaviors were examined. The apparent rates of dissolution and the release of the drug from Witepsol H-15 suppositories were significantly increased by the formation of inclusion complexes, particularly by DM-β-CyD. In addition, DM-β-CyD markedly inhibited the degradation of HCFU to give 5-fluorouracil in the small and rectal intestinal tracts. The plasma levels of HCFU after oral or rectal administration of the chemically stable and rapid dissolving form of DM-β-CyD complex to rabbits were significantly higher than those of the drug alone. The results indicate that the increase in oral or rectal bioavailability of HCFU by means of DM-β-CyD complexation may allow a reduction of the dose, which is a promising advantage for the decrease in side effects of anticancer agents.
