caa a22 4500 445312297 CHVBK 20180317142634.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1007/s11095-011-0396-7 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0396-7 Pharmacokinetic-Pharmacodynamic Disease Progression Model for Effect of Etanercept in Lewis Rats with Collagen-Induced Arthritis [Elektronische Daten] [Hoi-Kei Lon, Dongyang Liu, Qi Zhang, Debra DuBois, Richard Almon, William Jusko] ABSTRACT: Purpose: To develop a pharmacokinetic-pharmacodynamic disease progression (PK/PD/DIS) model to characterize the effect of etanercept in collagen-induced arthritis (CIA) rats on rheumatoid arthritis (RA) progression. Methods: The CIA rats received either 5 mg/kg intravenous (IV), 1 mg/kg IV, or 5 mg/kg subcutaneous (SC) etanercept at day 21 post-disease induction. Effect on disease progression was measured by paw swelling. Plasma concentrations of etanercept were assayed by enzyme-linked immunosorbent assay (ELISA). PK profiles were fitted first; parameter estimates were applied to fit paw edema data for PD and DIS-related parameter estimation using ADAPT 5 software. Results: The model contained a two-compartment PK model with Michaelis-Menten elimination. For SC administration, two additional mathematical functions for absorption were added. The disease progression component was an indirect response model with a time-dependent change in paw edema production rate constant (k in) assumed to be inhibited by etanercept. Conclusions: Etanercept has modest effects on paw swelling in CIA rats. The PK and PD profiles were well described by the developed PK/PD/DIS model, which may be used for other anti-cytokine biologic agents for RA. Springer Science+Business Media, LLC, 2011 arthritis nationallicence etanercept nationallicence model nationallicence pharmacodynamics nationallicence pharmacokinetics nationallicence Lon Hoi-Kei Department of Pharmaceutical Sciences School of Pharmacy & Pharmaceutical Sciences, University at Buffalo, 14260, Buffalo, New York, USA aut Liu Dongyang Department of Pharmaceutical Sciences School of Pharmacy & Pharmaceutical Sciences, University at Buffalo, 14260, Buffalo, New York, USA aut Zhang Qi Department of Pharmaceutical Sciences School of Pharmacy & Pharmaceutical Sciences, University at Buffalo, 14260, Buffalo, New York, USA aut DuBois Debra Department of Biological Sciences, University at Buffalo, 14260, Buffalo, New York, USA aut Almon Richard Department of Biological Sciences, University at Buffalo, 14260, Buffalo, New York, USA aut Jusko William Department of Pharmaceutical Sciences School of Pharmacy & Pharmaceutical Sciences, University at Buffalo, 14260, Buffalo, New York, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/7(2011-07-01), 1622-1630 0724-8741 28:7<1622 2011 28 11095 https://doi.org/10.1007/s11095-011-0396-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0396-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lon Hoi-Kei Department of Pharmaceutical Sciences School of Pharmacy & Pharmaceutical Sciences, University at Buffalo, 14260, Buffalo, New York, USA aut NATIONALLICENCE 700 1- Liu Dongyang Department of Pharmaceutical Sciences School of Pharmacy & Pharmaceutical Sciences, University at Buffalo, 14260, Buffalo, New York, USA aut NATIONALLICENCE 700 1- Zhang Qi Department of Pharmaceutical Sciences School of Pharmacy & Pharmaceutical Sciences, University at Buffalo, 14260, Buffalo, New York, USA aut NATIONALLICENCE 700 1- DuBois Debra Department of Biological Sciences, University at Buffalo, 14260, Buffalo, New York, USA aut NATIONALLICENCE 700 1- Almon Richard Department of Biological Sciences, University at Buffalo, 14260, Buffalo, New York, USA aut NATIONALLICENCE 700 1- Jusko William Department of Pharmaceutical Sciences School of Pharmacy & Pharmaceutical Sciences, University at Buffalo, 14260, Buffalo, New York, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/7(2011-07-01), 1622-1630 0724-8741 28:7<1622 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer