薬理と治療

Abstract

We performed comparative bioequivalence studies of the generic injectable epirubicindeveloped by Sawai and the branded product（Farmorubicin_）in cultured human tumor celllines and experimental tumor−bearing mouse models. Both products inhibited the proliferationof a variety of cultured malignant human cell lines, including THP−1 monocytic leukemia,UM−UC−3 bladder cancer, Hep G2 hepatocellular carcinoma, and the breast cancerMDA−MB−231 and SK−BR−3. Their IC50 values ranged from 9.8 to 639.4 ng／mL. The inhibitoryeffects of the two products on proliferation were biologically equivalent. To assess invivo antitumor activity, Sarcoma−180 or Ehrlich carcinoma was transplanted to mice i. p.（ascites tumor）or s. c.（solid tumor）and each product was administered i. v. on days 1, 5 and9 at 1.25 or 5.0 mg／kg／day. Administration of each product at 5.0 mg／kg was significantly butslightly prolonged survival time in Sarcoma−180 and Ehrlich ascites tumor−bearing mice.The increase of life span was 5.7−13.2％（1.25 mg／kg）and 22.2−34.3％（5.0 mg／kg）. In caseof the solid tumor−bearing mice, however, markedly inhibitory effects on tumor growth wereobserved at a dose of 1.25 or 5.0 mg／kg. The tumor inhibition rate was 38.1−44.8％（1.25 mg／kg）and 73.1−76.7％（5.0 mg／kg）. In ascites and solid tumor−bearing mice, antitumor activityof the two products was equivalent. These results show that epirubicin hydrochloride forinjection developed by Sawai is biologically equivalent to the innovator’s product.（Jpn Pharmacol Ther 2009；37：223−30）KEY WORDS Epirubicin hydrochloride, Farmorubicin, Antitumor activity, Bioequivalencestudy