Population pharmacokinetic data analysis of three phase I studies of matuzumab, a humanised anti-EGFR monoclonal antibody in clinical cancer development

A population pharmacokinetic model based on data from three phase I studies was to be developed including a covariate analysis to describe the concentration–time profiles of matuzumab, a novel humanised monoclonal antibody. Matuzumab was administered as multiple 1 h i.v. infusions with 11 different...

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Bibliographic Details
Published in:British journal of cancer 2008-03, Vol.98 (5), p.900-906
Main Authors: Kuester, K, Kovar, A, Lüpfert, C, Brockhaus, B, Kloft, C
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal - pharmacokinetics
Antibodies, Monoclonal, Humanized
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cancer therapies
Clinical Study
Clinical Trials, Phase I as Topic
Data analysis
Drug Resistance
Epidemiology
Epidermal growth factor
Female
Humans
Kinases
Male
Medical research
Medical sciences
Metastasis
Middle Aged
Models, Biological
Molecular Medicine
Monoclonal antibodies
Neoplasms - drug therapy
Oncology
Pharmacokinetics
Pharmacy
Tumors
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Summary:A population pharmacokinetic model based on data from three phase I studies was to be developed including a covariate analysis to describe the concentration–time profiles of matuzumab, a novel humanised monoclonal antibody. Matuzumab was administered as multiple 1 h i.v. infusions with 11 different dosing regimens ranging from 400 to 2000 mg, q1w–q3w. For analysis, 90 patients with 1256 serum concentration–time data were simultaneously fitted using the software NONMEM™. Data were best described using a two-compartment model with the parameters central ( V 1 ) and peripheral distribution volume ( V 2 ), intercompartmental ( Q ) and linear (CLL) clearance and an additional nonlinear elimination pathway ( K m , V max ). Structural parameters were in agreement with immunoglobulin characteristics. In total, interindividual variability on V max , CLL, V 1 and V 2 and interoccasion variability on CLL was 22–62% CV. A covariate analysis identified weight having an influence on V 1 (+0.44% per kg) and CLL (+0.87% per kg). All parameters were estimated with good precision (RSE
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6604265