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Population Pharmacokinetics of Rituximab (Anti-CD20 Monoclonal Antibody) in Rheumatoid Arthritis Patients During a Phase II Clinical Trial

From the Department of Pharmacokinetic and Pharmacodynamic Sciences, Genentech, Inc, South San Francisco, California (C. M. Ng, R. Bruno, D. Combs) and the Department of Clinical Pharmacology, Hoffmann-LaRoche, Inc, Nutley, New Jersey (B. Davies).

Rituximab is a B cell-depleting anti-CD20 chimeric IgG monoclonal antibody being investigated for the treatment of rheumatoid arthritis. The purpose of this study was to develop a population pharmacokinetic model in rheumatoid arthritis patients. In addition, the final pharmacokinetic model was used to assess the variability in drug exposure (AUC_0-) for fixed versus body surface area-based dosing. A total of 102 patients were included in this population pharmacokinetic analysis. A 2-compartment pharmacokinetic model described the data reasonably well. Body surface area and gender were the most significant covariates for both CL and Vc. Body surface area alone only explained about 19.7% of the total interindividual variability of CL. In a simulation study, body surface area-based dosing normalized drug exposure over a wide range of body surface area but did not seem to improve the predictability of rituximab AUC_0- in rheumatoid arthritis patients. Therefore, no rationale for body surface area-based dosing for rituximab in rheumatoid arthritis patients was found.

Key Words: Rituximab • rheumatoid arthritis • population pharmacokinetic model

Address for reprints: Chee M. Ng, PharmD, PhD, Department of Pharmacokinetic and Pharmacodynamic Sciences, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080-4990.

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