Objective: The purpose of this study was to evaluate the pharmacokinetics of etanercept in patients with ankylosing spondylitis (AS) in a phase 3 study.
Methods: Serum etanercept concentrations were analyzed from samples obtained at weeks 4 and 12 from 43 patients with AS (median age: 45 years; median body weight: 75 kg; white/non-white: 40/3; male/female: 34/9) receiving 25 mg subcutaneously twice weekly for 12 weeks. A population pharmacokinetics analysis using NONMEM was conducted to estimate individual etanercept pharmacokinetic parameters. Initially, appropriate base and covariate population pharmacokinetic models were built based on data from 10 prior clinical studies of etanercept administered subcutaneously or intravenously to healthy subjects (n = 53) and to patients with rheumatoid arthritis (RA) (n = 212). The influence of demographic characteristics on the pharmacokinetics of etanercept was thoroughly evaluated. The stability of the final model was evaluated using both internal (bootstrapping) and external (data splitting) validation approaches. Finally, the selected final population covariate model was used to estimate the Bayesian pharmacokinetic parameters for the patients with AS.
Results: The data from the 10 prior clinical studies were optimally fitted to a 2-compartment linear population covariate model. Both age (< 17 years) and body weight (< 60 kg) were found to be important covariates on clearance. Both bootstrapping and data splitting validated the population model. The mean Bayesian-predicted etanercept clearance and steady-state trough concentration were 0.072 l/h and 2,004 ng/ml, respectively. The pharmacokinetic parameters of etanercept in the patients with AS were similar to those observed in the patients with RA.
Conclusions: The pharmacokinetics of etanercept in patients with AS were similar to those in patients with RA. The AS disease state does not appear to alter the disposition of etanercept.