PURPOSE: To develop a pharmacokinetic-pharmacodynamic disease progression (PK/ @entity1726 /DIS) model to characterize the effect of etanercept in @entity1753 ( @entity1753 ) @entity35 on @entity309 ( @entity309 ) progression. METHODS: The @entity1753 @entity35 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 @entity4 data for @entity1726 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 @entity4 production rate constant (k(in)) assumed to be inhibited by etanercept. CONCLUSIONS: Etanercept has modest effects on paw swelling in @entity1753 @entity35 . The PK and @entity1726 profiles were well described by the developed PK/ @entity1726 /DIS model, which may be used for other anti-cytokine biologic agents for @entity309 .

Pharmacokinetic-pharmacodynamic disease progression model for effect of etanercept in Lewis @entity35 with XXXX .

@entity4 :: ('MESH:D004487', 'Disease') :: ['edema'] @entity1753 :: ('MESH:D001169', 'Disease') :: ['collagen-induced arthritis', 'CIA'] @entity1726 :: ('OMIM:168600', 'Disease') :: ['PD'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity309 :: ('MESH:D001172', 'Disease') :: ['rheumatoid arthritis', 'RA']
@entity1753 :: (MESH:D001169,Disease) :: ['collagen-induced arthritis']
