J Clin Pharmacol
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Sign In to gain access to subscriptions and/or personal tools.
First published on April 9, 2008, doi:10.1177/0091270008316886

The Journal of Clinical Pharmacology 2008;48:681.

This Article
Right arrow Full Text (JCP OnlineFirst[PDF])
Right arrow All Versions of this Article:
0091270008316886v1
48/6/681    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xu, Z.
Right arrow Articles by Zhou, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xu, Z.
Right arrow Articles by Zhou, H.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
©© 2008 American College of Clinical Pharmacology, Inc.
The Journal of Clinical Pharmacology , 10.1177/0091270008316886

Article

Population Pharmacokinetics of Infliximab in Patients With Ankylosing Spondylitis

Zhenhua Xu 1, Kathleen Seitz 1, Adedigbo Fasanmade 1, Joyce Ford 1, Paul Williamson 1, Weichun Xu 1, Hugh M. Davis 1, and Honghui Zhou 1*

1 Centocor Research and Development, Inc

* To whom correspondence should be addressed. E-mail: hzhou2{at}cntus.jnj.com.


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


This article has been cited by other articles:


Home page
 J Clin PharmacolHome page
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]

Home page
 J Clin PharmacolHome page
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]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2008 by the American College of Clinical Pharmacology