Pharmacokinetics and pharmacodynamics of FSK0808 and Gran after single intravenous drip administration or single subcutaneous administration: comparative study in healthy Japanese adult male subjects

摘要

FSK0808 is a recombinant human granulocyte colony-stimulating factor developed by Fuji Pharma Co., Ltd and Mochida Pharmaceutical Co., Ltd. as a biosimilar product of Gran ((R)). We verified the pharmacokinetic/pharmacodynamic equivalence of FSK0808 and commercially available Gran ((R)) by a randomized crossover study of single intravenous dose (200 mg/m(2)) and single subcutaneous dose (400 mg/m(2)) in healthy Japanese adult male subjects. According to the bioequivalence guidelines, the area under the blood concentration - time curve by 48 hours after administration (AUC(0-48)) in a single intravenous drip (IVD) study, and AUC(0-48) and maximum blood concentration (C-max) in a single subcutaneous (SC) dose study were used as primary endpoints, and the pharmacodynamic parameters including absolute neutrophil count (ANC) or number of CD34 positive cells (CD34(+) cells) as secondary endpoints. The safety was evaluated based on the characteristics and incidence of adverse reactions. As a result, the 90% confidence interval (CI) of the difference in mean value for AUC(0-48) among drugs ranged from log(0.8) to log(1.25), in the IVD study, and those for Cmax and AUC(0-48) were within the range of log(0.8)- log(1.25) in the SC study. Those for secondary endpoints were all within the range of log( 0.8)- log(1.25). Thus, the pharmacokinetics/pharmacodynamics of both drugs were considered equivalent for all routes of administration, and the profiles of adverse reactions were also very similar.