Bioequivalence of liquid and reconstituted lyophilized etanercept subcutaneous injections.
The objective of this study was to compare the pharmacokinetics of liquid and reconstituted lyophilized etanercept. This single-center, open-label study had a 2-period crossover design in which 36 healthy subjects were randomly assigned in a 1:1 ratio to etanercept (liquid/lyo or lyo/liquid). The treatments were separated by 28 days. Blood samples were obtained predose and at 10 predetermined time points postdose. Serum concentrations were determined by enzyme-linked immunosorbent assay. Noncompartmental pharmacokinetic parameters were analyzed using a standard crossover analysis of variance model. Thirty-three subjects completed both treatment periods. Geometric mean values (adjusted) of area under the serum drug concentration-time curve from time zero to the time of the final quantifiable sample, area under the serum drug concentration-time curve from time zero to infinity, and maximum concentration obtained with the 50-mg/mL liquid etanercept injection were 93.0%, 90.7%, and 98.5% of the respective parameters for 2 injections of 25 mg/mL reconstituted formulation. All associated confidence intervals were within the predefined equivalence interval of 80% to 125%. No differences in safety profiles of the 2 formulations were apparent. Liquid etanercept was bioequivalent to the reconstituted lyophilized etanercept formulation.
Sullivan
John T
JT
Amgen Inc, One Amgen Center Drive, Mailstop 38-4-C, Thousand Oaks, CA 91320, USA. jtsulliv@amgen.com
Ni
Liyun
L
Sheelo
Claudia
C
Salfi
Margaret
M
Peloso
Paul M
PM
D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D000068800:Etanercept; D005260:Female; D005612:Freeze Drying; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000009:adverse effects; D007279:Injections, Subcutaneous; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D013810:Therapeutic Equivalency
D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept