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


     

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Google Scholar
Google Scholar
Right arrow Articles by Zhu, Y.
Right arrow Articles by Zhou, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhu, Y.
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?

QUANTITATIVE CLINICAL PHARMACOLOGY

Population Pharmacokinetic Modeling of Ustekinumab, a Human Monoclonal Antibody Targeting IL-12/23p40, in Patients With Moderate to Severe Plaque Psoriasis

Yaowei Zhu, PhD, Chuanpu Hu, PhD, Ming Lu, PhD, Sam Liao, PhD, Joseph C. Marini, PhD, Jennifer Yohrling, PhD, Newman Yeilding, MD, Hugh M. Davis, PhD and Honghui Zhou, PhD, FCP

From Centocor Research and Development, Inc, Malvern, Pennsylvania (Drs Zhu, Hu, Lu, Marini, Yohrling, Yeilding, Davis, Zhou) and PharMax Research, Inc, Somerset, New Jersey (Dr Liao).

The population pharmacokinetics of ustekinumab are characterized in patients with moderate to severe plaque psoriasis in 2 Phase 3 studies (PHOENIX 1 and PHOENIX 2). Serum concentration data from 1937 patients are analyzed to determine pharmacokinetic characteristics of ustekinumab and to assess factors that may contribute to their variability. The population typical mean (percentage relative standard error) values for apparent clearance, apparent volume of distribution, and absorption rate constant from the final covariate model are 0.465 L·day-1 (2.0%), 15.7 L (2.0%), and 0.354 day-1 (16.2%), respectively. The interindividual variabilities for apparent clearance and apparent volume of distribution are 41.0% and 33.2%, respectively. Of the factors evaluated in this analysis, body weight, diabetes, and positive immune response (antibodies to ustekinumab) are important covariates affecting the apparent clearance and/or apparent volume of distribution of ustekinumab. To fully understand the clinical relevance of these results, the covariate findings need to be evaluated concurrently with the efficacy and safety data.

Key Words: Interleukin-12 and Interleukin-23 p40 • monoclonal antibody • ustekinumab • population pharmacokinetic modeling • psoriasis

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


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?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2009 by the American College of Clinical Pharmacology