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Population pharmacokinetics of ustekinumab in patients with active psoriatic arthritis.

Author(s): Zhu YW, Mendelsohn A, Pendley C, Davis HM, Zhou H

Affiliation(s): Pharmacokinetics, Modeling and Simulation, Biologics Clinical Pharmacology, Centocor Research & Development, Inc., 200 Great Valley Parkway, Malvern, PA 19355, USA. yzhu8@its.jnj.com

Publication date & source: 2010-12, Int J Clin Pharmacol Ther., 48(12):830-46.

Publication type: Clinical Trial, Phase II; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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 (ka) obtained from the final covariate model were 0.465 l x 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.

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