Model-based assessment of erlotinib effect in vitro measured by real-time cell analysis
作者： Stephan Benay , Christophe Meille , Stefan Kustermann , Isabelle Walter , Antje Walz
DOI: 10.1007/S10928-015-9415-3
关键词: Biophysics 、 Cell growth 、 Epidermoid carcinoma 、 Chemistry 、 Pharmacology 、 Potency 、 Cell killing 、 Pharmacokinetics 、 Pharmacodynamics 、 Erlotinib 、 Population
摘要: Real time cell analysis (RTCA) is an impedance-based technology which tracks various living characteristics over time, such as their number, morphology or adhesion to the extra cellular matrix. However, there no consensus about how RTCA data should be used quantitatively evaluate pharmacodynamic parameters describe drug efficacy toxicity. The purpose of this work was determine can analyzed with mathematical modeling explore and quantify effect in vitro. pharmacokinetic-pharmacodynamic erlotinib concentration profile predicted by model its on human epidermoid carcinoma line A431 vitro measured through output, designated index. A population approach estimate parameter values, considering a plate well statistical unit. related index number cells means proportionality factor. Cell growth described exponential model. delay between pharmacokinetics killing transit compartment model, potency, E max function concentration. performed distinguished effects from other likely modify relationship number. It also revealed time-dependent decrease mono-exponential pharmacokinetic nonspecific binding.
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