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Population pharmacokinetics of infliximab in patients with ankylosing spondylitis.

Author(s): Xu Z, Seitz K, Fasanmade A, Ford J, Williamson P, Xu W, Davis HM, Zhou H

Affiliation(s): Pharmacokinetics, Modeling & Simulation, Clinical Pharmacology Sciences, Centocor Research and Development, Inc., 200 Great Valley Parkway, Malvern, PA 19355, USA.

Publication date & source: 2008-06, J Clin Pharmacol., 48(6):681-95. Epub 2008 Apr 9.

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

The population pharmacokinetics of infliximab were characterized in patients with active ankylosing spondylitis (n = 274). Serum infliximab concentration data, from a 2-year period, were analyzed using NONMEM. A 2-compartment linear pharmacokinetic model was chosen to describe the pharmacokinetic characteristics of infliximab in serum. Population estimates (typical value +/- standard error) were obtained from the final covariate model: clearance (CL: 0.273 +/- 0.007 L/day), volume of distribution in the central compartment (V(1): 3.06 +/- 0.057 L), intercompartment clearance (Q: 1.72 +/- 0.48 L/day), and volume of distribution in the peripheral compartment (V(2): 2.94 +/- 0.17 L). Interindividual variability for CL and V(1) was 34.1% and 17.5%, respectively. White blood cell count at baseline and the antibody-to-infliximab status were significant covariates to CL; body surface area and sex were significant covariates to V(1). The CL for patients with a positive antibody-to-infliximab status was estimated to be 41.9% to 76.7% higher than for the remaining patients. Other covariates (baseline disease activity and the concomitant medication use of prednisolone, omeprazole, nonsteroidal anti-inflammatory drugs, or analgesics) did not affect infliximab pharmacokinetics. The development of antibodies to infliximab was associated with accelerated infliximab clearance and may represent a potential underlying mechanism for an inadequate response, or loss of response, to infliximab treatment.

Page last updated: 2008-11-03

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