Population Pharmacokinetics of Rituximab (Anti‐CD20 Monoclonal Antibody) in Rheumatoid Arthritis Patients During a Phase II Clinical Trial
- 1 July 2005
- journal article
- clinical trial
- Published by Wiley in The Journal of Clinical Pharmacology
- Vol. 45 (7), 792-801
- https://doi.org/10.1177/0091270005277075
Abstract
Rituximab is a B cell-depleting anti-CD20 chimeric IgGkappa 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 (AUC0-infinity) 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 AUC0-infinity in rheumatoid arthritis patients. Therefore, no rationale for body surface area-based dosing for rituximab in rheumatoid arthritis patients was found.Keywords
This publication has 15 references indexed in Scilit:
- Efficacy of B-Cell–Targeted Therapy with Rituximab in Patients with Rheumatoid ArthritisThe New England Journal of Medicine, 2004
- Rituximab therapy and autoimmune disorders: Prospects for anti–B cell therapyArthritis & Rheumatism, 2003
- Pharmacokinetic study of patients with follicular or mantle cell lymphoma treated with rituximab as ‘in vivo purge’ and consolidative immunotherapy following autologous stem cell transplantationAnnals of Oncology, 2003
- RituximabDrugs, 2003
- Clinical outcome in 22 patients with rheumatoid arthritis treated with B lymphocyte depletionAnnals Of The Rheumatic Diseases, 2002
- Efficacy of selective B cell blockade in the treatment of rheumatoid arthritis: Evidence for a pathogenetic role of B cellsArthritis & Rheumatism, 2002
- Sustained improvement in rheumatoid arthritis following a protocol designed to deplete B lymphocytesRheumatology, 2001
- Use of rituximab, the new FDA-approved antibodyCurrent Opinion in Oncology, 1998
- Association of serum Rituximab (IDEC–C2B8) concentration and anti-tumor response in the treatment of recurrent low-grade or follicular non-Hodgkin’s lymphomaAnnals of Oncology, 1998
- CLINICAL CALORIMETRYArchives of Internal Medicine, 1916