薬理と治療

Abstract

Objectives ESUEEWAN(R) combination capsule（SW651K）is a generic oral anticancer drug of S-1 combination capsule. We examined the combination effect of 5-chloro-2,4-dihydroxypyridine（CDHP）and potassium oxonate（Oxo）in SW651K and the possibility of gastrointestinal tract injury under the condition to show an antitumor activity, and not to develop a diarrhea in Yoshida sarcoma-bearing rat model. Methods To confirmed the effects of CDHP and Oxo in the commercial formulation of SW651K, we investigated the interactive pharmacological effects of SW651K without CDHP （CDHP－）and SW651K without Oxo（Oxo－）, prepared according to commercial methods. These formulations were orally administered to Yoshida sarcoma-bearing rats. The pharmacokinetic profiles of tegafur（FT）, 5-fluorouracil（5-FU）, CDHP, Oxo, and α-fluoro-β-alanine （FBAL）were compared after a single dose of either SW651K or CDHP－. Antitumor effect was evaluated on the basis of tumor volume after treatment for 7 consecutive days. The effects of Oxo on enterotoxicity were evaluated on the basis of body weights, incidence of diarrhea, pathological findings, the length and weight of intestinal tissue after consecutive treatments. Results Antitumor effect was significantly increased by the addition of CDHP, which was associated with an increased 5-FU concentration in blood and tumor. Furthermore, the plasma FBAL increased with a decrease in the plasma CDHP. Oxo suppressed the diarrhea completely, but did not all other evaluation items completely. Conclusions These results suggested that it is important to carefully monitor patients for side effects in clinical practice under the condition to show an antitumor activity, and not to develop a diarrhea.