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Updated: May 14, 2026

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
Published on: April 6, 2016
Preclinical pharmacokinetic/pharmacodynamic models to predict schedule-dependent interaction between erlotinib and
Mengyao Li1, Hanqing Li, Xiaoliang Cheng
1Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Purpose:
To investigate the pharmacological effects of different erlotinib (ER) and gemcitabine (GM) combination schedules by in vitro and in vivo experiments and PK/PD models in non-small cell lung cancer cells.
Methods:
H1299 cells were exposed to different ER combined with GM schedules. Cell growth inhibition was analyzed to evaluate these schedules. A preclinical in vivo study was then conducted to compare tumor suppression effects of different schedules in H1299 xenografts. PK/PD models were developed to quantify the anti-tumor interaction of ER and GM.
Results:
Synergism was observed when ER preceded GM, but other sequences showed antagonism. The optimal in vitro schedule, or interval schedule, was applied to the animal study, which showed greater anti-tumor effect than simultaneous group. PK/PD models implied that interaction of the two drugs was additive in simultaneous treatment but synergistic in interval schedule. The simulation results showed that interval schedule can delay tumor growth for a longer time, and demonstrated more evident anti-tumor effect compared with simultaneous group if the treatment duration was longer.
Conclusions:
Interval schedule of the two drugs can achieve synergistic anti-tumor effect, and is superior to simultaneous treatment.
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