Population pharmacokinetics of cetuximab in patients with squamous cell carcinoma of the head and neck

Nathanael L. Dirks, Arno Nolting, Andreas Kovar, Bernd Meibohm

Research output: Contribution to journalArticle

53 Citations (Scopus)

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 V max 4.38 mg/h (15.4%), K m 74 μg/mL, central compartment volume V 1 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 V max and total body weight as a predictor of V 1 . 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.

Original languageEnglish (US)
Pages (from-to)267-278
Number of pages12
JournalJournal of Clinical Pharmacology
Volume48
Issue number3
DOIs
StatePublished - Mar 1 2008

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Pharmacokinetics
Ideal Body Weight
Population
Body Weight
Body Surface Area
Leukocyte Count
Epidermal Growth Factor Receptor
Therapeutics
Monoclonal Antibodies
Cetuximab
Carcinoma, squamous cell of head and neck

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Population pharmacokinetics of cetuximab in patients with squamous cell carcinoma of the head and neck. / Dirks, Nathanael L.; Nolting, Arno; Kovar, Andreas; Meibohm, Bernd.

In: Journal of Clinical Pharmacology, Vol. 48, No. 3, 01.03.2008, p. 267-278.

Research output: Contribution to journalArticle

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