J Clin Pharmacol
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0091270009339192v1
49/9/1056    most recent
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SPECIAL POPULATIONS

Population Pharmacokinetics of Golimumab, an Anti–Tumor Necrosis Factor-{alpha} Human Monoclonal Antibody, in Patients With Psoriatic Arthritis

Zhenhua Xu, PhD, FCP, Thuy Vu, PharmD, Howard Lee, MD, PhD, Chuanpu Hu, PhD, Jie Ling, PhD, Hong Yan, MPH, MD, Daniel Baker, MD, Anna Beutler, MD, Charles Pendley, PhD, Carrie Wagner, PhD, Hugh M. Davis, PhD and Honghui Zhou, PhD, FCP

From Centocor Research and Development, Malvern, Pennsylvania (Dr Xu, Dr Hu, Dr Ling, Dr Yan, Dr Baker, Dr Beutler, Dr Pendley, Dr Wagner, Dr Davis, Dr Zhou); and the Center for Drug Development Science, Department of Biopharmaceutical Sciences, University of California–San Francisco, Washington, DC (Dr Vu, Dr Lee). Drs. Xu and Vu contributed equally to this work.

The population pharmacokinetics of subcutaneously administered golimumab (50 mg or 100 mg every 4 weeks) were characterized in patients with active psoriatic arthritis (PsA) in GO-REVEAL, a randomized, double-blind, placebo-controlled, phase 3 study. A total of 2029 serum golimumab concentrations from 337 patients were analyzed using NONMEM. A 1-compartment pharmacokinetic model with first-order absorption and elimination was chosen to describe the observed concentration–time data. For a patient of standard weight (70 kg), the population estimates (typical value ± standard error) for golimumab pharmacokinetic parameters were as follows: apparent clearance = 1.38 ± 0.04 L/d, apparent volume of distribution = 24.9 ± 1.04 L, and absorption rate constant = 0.908 ± 0.121 per day. The between-subject variability was 37.6% in apparent clearance and 37.9% in apparent volume of distribution. Body weight, antibody-to-golimumab status, baseline C-reactive protein level, and smoking status were identified as significant covariates on apparent clearance. Body weight was also a significant covariate on apparent volume of distribution. None of the concomitant medications examined (methotrexate, corticosteroids, and nonsteroidal anti-inflammatory drugs) were significant covariates on apparent clearance, although the median trough golimumab concentration in patients receiving methotrexate was higher than for those not receiving methotrexate. These significant covariates account for part of the variability in systemic exposure to golimumab observed in patients with PsA.

Key Words: Tumor necrosis factor • monoclonal antibody • golimumab • population pharmacokinetics • psoriatic arthritis

Address for reprints: Honghui Zhou, PhD, FCP, Centocor Research and Development, 200 Great Valley Parkway, Malvern, PA 19355; e-mail: hzhou2{at}its.jnj.com.


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