Population pharmacokinetic data analysis of three phase I studies of matuzumab, a humanised anti-EGFR monoclonal antibody in clinical cancer development
British Journal of Cancer, ISSN: 0007-0920, Vol: 98, Issue: 5, Page: 900-906
2008
- 22Citations
- 27Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Metrics Details
- Citations22
- Citation Indexes22
- 22
- CrossRef20
- Captures27
- Readers27
- 27
Article Description
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) and peripheral distribution volume (V), intercompartmental (Q) and linear (CLL) clearance and an additional nonlinear elimination pathway (K, V). Structural parameters were in agreement with immunoglobulin characteristics. In total, interindividual variability on V, CLL, V and V and interoccasion variability on CLL was 22-62% CV. A covariate analysis identified weight having an influence on V (+0.44% per kg) and CLL (+0.87% per kg). All parameters were estimated with good precision (RSE<39%). A robust population pharmacokinetic model for matuzumab was developed, including a nonlinear pharmacokinetic process. In addition, relevant and plausible covariates were identified and incorporated into the model. When correlated to efficacy, this model could serve as a tool to guide dose selection for this 'targeted' cancer therapy. © 2008 Cancer Research UK.
Bibliographic Details
Springer Science and Business Media LLC
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