Investigation of bioequivalence between brand-name and generic irinotecan products

Abstract

Background/Aim: To investigate bioequivalence among generic and brand-name irinotecan products. Materials and Methods: Products of Yakult and Daiichi-Sankyo (brandname products), Sandoz, Nippon Kayaku, Taiho, and Sawai were compared with respect to their composition and antitumor activity. Results: High-performance liquid chromatography demonstrated that related substances were within the acceptable range. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay revealed significant differences in cytotoxicity for four cancer cell lines among the products. The concentration of the active compound SN-38 was highest in Yakult's product (23.82 ng/ml) and lowest in Daiichi-Sankyo's product (8.96 ng/ml). MTT assay data were correlated with the SN-38 concentration, suggesting that it influenced differences in cytocidal activity among products. However, the SN-38 concentration was far lower than that of irinotecan (20 mg/ml), suggesting a negligible clinical effect. Metabolism of irinotecan to SN-38 or open-ring forms did not differ significantly among the products. Conclusion: The generic products showed equivalent efficacy and safety to the brand-name products.