BIOEQUIVALENCE STUDY OF THE BIOSIMILAR RECOMBINANT HUMAN ERYTHROPOIETIN ALPHA (RENOGEN®) AND EPREX® AFTER SUBCUTANEOUS ADMINISTRATION

ABSTRACT

To determine the bioequivalence of two formulations of recombinant human erythropoietin alpha (epoetin alpha 4000-IU), the two formulations; Renogen® and the Reference, Eprex® were administered to 18 healthy Thai male volunteers as a single subcutaneous dose according to a randomized two-way crossover design. Serial blood samples were collected over a period of 96 hours. The pharmacokinetic parameters were analyzed by noncompartmental analysis, and bioequivalence analysis (ANOVA) was carried out using logarithmically transformed data of the AUC, Cmax and untransformed Tmax. The elimination half-life of the test product (28.7 h) and the reference (31.1 h) were comparable. The median Tmax of the test product (12.0 h, range 4-15 h) was slightly slower than that of the reference (11.0 h, range 8-15 h). The ANOVA showed no statistically significant differences between the AUC and Cmax values or between the test and the reference preparations. The mean (90% CI) for the ratios Test/Reference for AUC0-t, AUC0-∞ and Cmax were 1.03 (0.97-1.10), 1.01 (0.96-1.06) and 0.99 (0.90-1.08), respectively, within the bioequivalence range of 0.80-1.25. The study concluded that the test product is bioequivalent to the reference.