Journal of Bioequivalence & Bioavailability

Abstract

Bioequivalence Studies of A Generic Formulation (SW651K) to the Brand Drug S-1 in Tumor-Bearing Rat Models

Tomoyuki Okabe, Takeharu Ogura, Takashi Yoshimura, Yoshiyuki Tanaka, Hiromu Toyoda, Ken-ichi Fujita and Yasutsuna Sasaki

SW651K, a fixed combination of tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo), is a generic preparation of S-1, which is widely used to treat gastric cancer in Japan. There is little detailed information of pharmacological effects of SW651K in clinical therapy. However it is not easy to evaluate the PK/PD in clinical trial. Therefore this study examined the bioequivalence of SW651K to S-1 in terms of pharmacokinetics and tumor shrinkage in tumor-bearing rats. Bioequivalence of SW651K to S-1 was first evaluated in Yoshida sarcomabearing rats. Concentrations of FT, 5-fluorouracil (5-FU, the active metabolite of FT), CDHP, and Oxo in plasma, tumor, small intestine, and large intestine were analyzed after a single dose of SW651K. Tumor size was measured during treatment with each formulation for 7 consecutive days. Next, tumor size was measured in human gastric cancer cell (NUGC4)-bearing rats treated for 14 days. Tumor 5-FU concentrations were also analyzed. Tumor size in NUGC4-bearing rats treated with SW651K or S-1 plus cisplatin was also evaluated. SW651K was bioequivalent to S-1 in terms of the pharmacokinetics of all components and of 5-FU in rats. Both formulations also had equivalent antitumor activities in Yoshida sarcoma- and NUGC4 tumor-bearing rats that received monotherapy. Moreover, combined treatment with cisplatin equally potentiated the antitumor effects of both formulations, without increasing body-weight loss in NUGC4 tumor-bearing rats. In conclusion, bioequivalence of SW651K and S-1 was confirmed in terms of pharmacokinetics and antitumor effectiveness in tumor-bearing rats. Our results suggest that SW651K is clinically equivalent to S-1.