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 January 24, 2008, doi:10.1177/0091270007313393

The Journal of Clinical Pharmacology 2008;48:267.

This Article
Right arrow Full Text (JCP OnlineFirst[PDF])
Right arrow All Versions of this Article:
0091270007313393v1
48/3/267    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 Dirks, N. L.
Right arrow Articles by Meibohm, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dirks, N. L.
Right arrow Articles by Meibohm, B.
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 , 10.1177/0091270007313393

Article

Population Pharmacokinetics of Cetuximab in Patients With Squamous Cell Carcinoma of the Head and Neck

Nathanael L. Dirks 1, Arno Nolting 2, Andreas Kovar 2, and Bernd Meibohm 1*

1 University of Tennessee Health Science Center
2 Merck KGaA

* To whom correspondence should be addressed. E-mail: bmeibohm{at}utmem.edu.


  Abstract
Cetuximab is a monoclonal antibody directed against the epidermal growth factor receptor and is indicated in the treatment of squamous cell carcinoma of the head and neck. The population pharmacokinetics of cetuximab were characterized by nonlinear mixed effects modeling (NONMEM V) using a total of 912 concentrations from 143 patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck enrolled in 2 phase I/II studies. Cetuximab pharmacokinetics were best described by a 2-compartment model with Michaelis-Menten-type saturable elimination. Population estimates (between-subject variability, percent coefficient of variation) of the pharmacokinetic parameters were Vmax 4.38 mg/h (15.4%), Km 74 µg/mL, central compartment volume V1 2.83 L (18.6%), peripheral compartment volume 2.43 L (56.4%), and intercompartmental clearance 0.103 L/h (97.2%). Ideal body weight and white blood cell count were identified as predictors of Vmax and total body weight as a predictor of V1. Clinical dose adjustments beyond the approved body surface area–based dosing of cetuximab may be warranted in patients with extreme deviations of their actual body weight from ideal body weight. Agreement between simulated and measured concentrations monitored for up to 43 weeks of therapy indicates that cetuximab pharmacokinetic parameters remained constant during prolonged therapy.
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 page
 JCOHome page
J. Thariat, N. Azzopardi, F. Peyrade, V. Launay-Vacher, J. Santini, T. Lecomte, M.-C. Etienne-Grimaldi, G. Paintaud, and G. Milano
Cetuximab Pharmacokinetics in End-Stage Kidney Disease Under Hemodialysis
J. Clin. Oncol., September 1, 2008; 26(25): 4223 - 4225.
[Full Text] [PDF]


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