[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.