Abstract

Purpose: To characterize the population pharmacokinetics of subcutaneous ustekinumab, a human IgG1Kappa; monoclonal antibody against interleukin-12/23p40, using data from a randomized, double-blind, placebo-controlled Phase II study in patients with active psoriatic arthritis (PsA). Methods: A total of 786 quantifiable serum ustekinumab concentrations from 130 patients were analyzed using a nonlinear mixed-effects modeling approach. A 1-compartment model with first-order absorption and elimination was selected as the structural model. Results: The population typical mean (percent relative standard error (%RSE)) values for apparent clearance (CL/F), apparent volume of distribution (V/F), and absorption rate constant (k_a) obtained from the final covariate model were 0.465 l × day–1 (5.1%), 14.3 l (4.4%), and 0.427 day–1 (3.9%), respectively. The between-subject variability in CL/F, V/F, and ka were 53.9%, 42.3%, and 82.4%, respectively. Patient body weight and antibody-to-ustekinumab status were significant covariates affecting the CL/F and/or V/F of ustekinumab. None of the other factors evaluated, such as age, sex, race, baseline disease characteristics, concomitant methotrexate or nonsteroidal anti-inflammatory drugs, and past use of immunosuppressives, biologics, systemic corticosteroids, or disease-modifying antirheumatic drugs, were found to have significant effects on the pharmacokinetics of ustekinumab. Conclusion: The pharmacokinetics of ustekinumab in patients with PsA are comparable to those in patients with moderate-to-severe plaque psoriasis which was previously investigated.

Author Details

Authors

• Y.W. Zhu
• A. Mendelsohn
• C. Pendley
• H.M. Davis
• H. Zhou

Departments

• Centocor Research & Development, Inc., Malvern, PA, USA

Address

Y.W. Zhu, PhD
Pharmacokinetics, Modeling and Simulation, Biologics Clinical Pharmacology
Centocor Research & Development, Inc.
200 Great Valley Parkway
Malvern, PA 19355, USA
Email: [email protected]

Citation