Michaelis-Menten elimination kinetics of etanercept, rheumatoid arthritis biologics, after intravenous and subcutaneous administration in rats.

Abstract

Etanercept was approved by the Food and Drug Administration (FDA) in 2010 as a biologic agent for the treatment of rheumatoid arthritis (RA). The aim of the study was to investigate the pharmacokinetic properties of etanercept after intravenous and subcutaneous injection in rats. The plasma concentration of etanercept was determined using an enzyme-linked immunosorbent assay (ELISA). Intravenous and subcutaneous administration of 2mg/kg of etanercept to rats showed that etanercept was slowly absorbed (time to reach the peak drug concentration [T max]=1.60days, bioavailability [F]=47.18%) and slowly eliminated (half-life [t 1/2], 2.33days after intravenous administration and 3.31days after subcutaneous administration). The area under the curve values on day 13 (AUC13day) were 121.25±14.37 and 48.56±6.78μgday/mL after intravenous and subcutaneous administration, respectively. A two-compartment model with Michaelis-Menten elimination kinetics (V max=94.28µg/day; K m=10.88µg/mL) was used to describe the pharmacokinetic profile of etanercept. Our results describe the pharmacokinetic profile of etanercept, and these results could be used for the development of etanercept biosimilars.