HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) All Versions of this Article: 0091270008316886v1 48/6/681    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Xu, Z. Articles by Zhou, H. Search for Related Content PubMed PubMed Citation Articles by Xu, Z. Articles by Zhou, H. Social Bookmarking                         What's this?

Population Pharmacokinetics of Infliximab in Patients With Ankylosing Spondylitis

From Centocor Research and Development, Inc., Malvern, Pennsylvania.

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 (V₁: 3.06 ± 0.057 L), intercompartment clearance (Q: 1.72 ± 0.48 L/day), and volume of distribution in the peripheral compartment (V₂: 2.94 ± 0.17 L). Interindividual variability for CL and V₁ 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 V₁. 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.

Key Words: Human anti-TNF- monoclonal antibody • infliximab • population pharmacokinetics • ankylosing spondylitis

Address for reprints: Honghui Zhou, PhD, FCP, Pharmacokinetics, Modeling & Simulation, Clinical Pharmacology Sciences, Centocor Research and Development, Inc., 200 Great Valley Parkway, Malvern, PA 19355; e-mail: hzhou2{at}cntus.jnj.com.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C H Seow, A Newman, S P Irwin, A H Steinhart, M S Silverberg, and G R Greenberg Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis Gut, January 1, 2010; 59(01): 49 - 54. [Abstract] [Full Text] [PDF]

				J. Ling, H. Zhou, Q. Jiao, and H. M. Davis Interspecies Scaling of Therapeutic Monoclonal Antibodies: Initial Look J. Clin. Pharmacol., December 1, 2009; 49(12): 1382 - 1402. [Abstract] [Full Text] [PDF]

				P. Ma, B.-B. Yang, Y.-M. Wang, M. Peterson, A. Narayanan, L. Sutjandra, R. Rodriguez, and A. Chow Population Pharmacokinetic Analysis of Panitumumab in Patients With Advanced Solid Tumors J. Clin. Pharmacol., October 1, 2009; 49(10): 1142 - 1156. [Abstract] [Full Text] [PDF]

				D. D. Wang, S. Zhang, H. Zhao, A. Y. Men, and K. Parivar Fixed Dosing Versus Body Size-Based Dosing of Monoclonal Antibodies in Adult Clinical Trials J. Clin. Pharmacol., September 1, 2009; 49(9): 1012 - 1024. [Abstract] [Full Text] [PDF]