HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) 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 ISI Web of Science 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 ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Sun, Y.-N. Articles by Bruno, R. A. Search for Related Content PubMed PubMed Citation Articles by Sun, Y.-N. Articles by Bruno, R. A. Social Bookmarking                   What's this?

Population Pharmacokinetics of Efalizumab (Humanized Monoclonal Anti-CD11a Antibody) Following Long-Term Subcutaneous Weekly Dosing in Psoriasis Subjects

From the Department of Pharmacokinetic and Pharmacodynamic Sciences (Dr Sun, Dr Lu, Dr Joshi, Dr Bruno), Department of Specialty Biotherapeutics (Dr Kwon), and Biostatistics (Mr Compton), Genentech, Inc, South San Francisco, California.

The population pharmacokinetics of efalizumab was characterized in patients with moderate to severe plaque psoriasis. The study included 1088 subjects who received 1 or 2 mg/kg/wk subcutaneous efalizumab for 12 weeks from a phase I (64 subjects) and 3 phase III studies with day 42 and/or day 84 trough levels (1024 patients). Due to the limitation of the data, a 1-compartment model with first-order absorption and elimination was used to fit the data. The population means for V/F, Ka, and CL/F were 9.13 L, 0.191 day^-1, and 1.29 L/d, respectively, for a typical subject receiving a 1-mg/kg dose. Interindividual variability in CL/F was 48.2%. Body weight has the largest influence on CL/F. Other covariates (obesity, baseline lymphocyte counts, Psoriasis Area and Severity Index score, and age) had only modest effects. Subjects in the 2-mg/kg dose group had a 24.0% lower CL/F, consistent with nonlinear pharmacokinetics of efalizumab. The results of this analysis support the current body weight-adjusted dosing strategy.

Key Words: Efalizumab • psoriasis • population pharmacokinetics • nonlinear mixed effect modeling • NONMEM analysis • Psoriasis Area and Severity Index (PASI) score

Address for reprints: Amita Joshi, PhD, Late Stage BioTherapeutics, Department of Pharmacokinetic and Pharmacodynamic Sciences, MS 70, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080.

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

This article has been cited by other articles:

				Y. Zhu, C. Hu, M. Lu, S. Liao, J. C. Marini, J. Yohrling, N. Yeilding, H. M. Davis, and H. Zhou Population Pharmacokinetic Modeling of Ustekinumab, a Human Monoclonal Antibody Targeting IL-12/23p40, in Patients With Moderate to Severe Plaque Psoriasis J. Clin. Pharmacol., February 1, 2009; 49(2): 162 - 175. [Abstract] [Full Text] [PDF]

				Z. Xu, K. Seitz, A. Fasanmade, J. Ford, P. Williamson, W. Xu, H. M. Davis, and H. Zhou Population Pharmacokinetics of Infliximab in Patients With Ankylosing Spondylitis J. Clin. Pharmacol., June 1, 2008; 48(6): 681 - 695. [Abstract] [Full Text] [PDF]

				B. Joos, A. Trkola, H. Kuster, L. Aceto, M. Fischer, G. Stiegler, C. Armbruster, B. Vcelar, H. Katinger, and H. F. Gunthard Long-Term Multiple-Dose Pharmacokinetics of Human Monoclonal Antibodies (MAbs) against Human Immunodeficiency Virus Type 1 Envelope gp120 (MAb 2G12) and gp41 (MAbs 4E10 and 2F5). Antimicrob. Agents Chemother., May 1, 2006; 50(5): 1773 - 1779. [Abstract] [Full Text] [PDF]

				A. Joshi, R. Bauer, P. Kuebler, M. White, C. Leddy, P. Compton, M. Garovoy, P. Kwon, P. Walicke, and R. Dedrick An Overview of the Pharmacokinetics and Pharmacodynamics of Efalizumab: A Monoclonal Antibody Approved for Use in Psoriasis J. Clin. Pharmacol., January 1, 2006; 46(1): 10 - 20. [Abstract] [Full Text] [PDF]