[Influence of immunopotentiators on the activation of 5-FU derivatives].
As it has been shown that various kinds of immunopotentiators inhibit the hepatic microsomal drug-metabolizing enzymes and reduce the activation of masked compounds such as tegafur, we investigated the influence of immunopotentiators (OK-432 and PSK) on the activation of carmofur (HCFU), which is known to be transformed spontaneously in to the tumor-active substance, 5-fluorouracil (5-FU), in vivo, and compared the results to those obtained for tegafur. After oral administration of tegafur, the area under the plasma concentration curves of 5-FU in rats pretreated with OK-432 and PSK were 72% and 79% of those in untreated rats, while in the case of HCFU almost similar plasma concentration curves for 5-FU were obtained in both treated and untreated rats. These results show that the activation of HCFU to 5-FU is not influenced by treatment with these immunopotentiators. Furthermore, our clinical investigation showed that the survival curves of cancer patients given combination therapy of tegafur with OK-432 tended to be lower than those given a single therapy of tegafur, supporting the above mentioned basic results.
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001688:Biological Products / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010844:Picibanil / Q000494:pharmacology*; D011509:Proteoglycans / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D005641:Tegafur / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D001688:Biological Products; D011509:Proteoglycans; D005641:Tegafur; D010844:Picibanil; C010770:polysaccharide-K; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; C017367:carmofur; D005472:Fluorouracil