Michaelis-Menten elimination kinetics of etanercept, rheumatoid arthritis biologics, after intravenous and subcutaneous administration in rats.
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 2 mg/kg of etanercept to rats showed that etanercept was slowly absorbed (time to reach the peak drug concentration [T max] = 1.60 days, bioavailability [F] = 47.18 %) and slowly eliminated (half-life [t 1/2], 2.33 days after intravenous administration and 3.31 days after subcutaneous administration). The area under the curve values on day 13 (AUC13day) were 121.25 ± 14.37 and 48.56 ± 6.78 μg day/mL after intravenous and subcutaneous administration, respectively. A two-compartment model with Michaelis-Menten elimination kinetics (V max = 94.28 µg/day; K m = 10.88 µg/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.
College of Pharmacy, Chungnam National University, Daehak-ro 79, Yousung-gu, Daejeon, 305-764, Republic of Korea.
Byung-Yo
BY
Lee
College of Pharmacy, Chungnam National University, Daehak-ro 79, Yousung-gu, Daejeon, 305-764, Republic of Korea.
Kwang-Il
KI
Kwon
College of Pharmacy, Pusan National University, 2, Busandaehak-ro 63 beon-gil, Geumjeong-gu, Busan, 609-735, Republic of Korea. minsookim@pusan.ac.kr.
Min-Soo
MS
Kim
College of Pharmacy, Kyungsung University, 309 Suyeong-ro, Nam-gu, Busan, 608-736, Republic of Korea. baek@ks.ac.kr.
In-Hwan
IH
Baek
D000279:Administration, Cutaneous; D061605:Administration, Intravenous / Q000379:methods; D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001682:Biological Availability; D059451:Biosimilar Pharmaceuticals / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000068800:Etanercept / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous / Q000379:methods; D007700:Kinetics; D051381:Rats
D018501:Antirheumatic Agents; D059451:Biosimilar Pharmaceuticals; D000068800:Etanercept
Etanercept; Michaelis–Menten kinetics; Pharmacokinetics; Subcutaneous