Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Pharm Res. 2013 May;30(5):1400-8. doi: 10.1007/s11095-013-0978-7. Epub 2013 Jan 24.
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.
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.
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.
Interval schedule of the two drugs can achieve synergistic anti-tumor effect, and is superior to simultaneous treatment.
通过体外和体内实验以及药代动力学/药效学（PK/PD）模型研究不同厄洛替尼（ER）联合吉西他滨（GM）方案在非小细胞肺癌细胞中的药理作用。
将 H1299 细胞暴露于不同的 ER 联合 GM 方案中。通过分析细胞生长抑制来评估这些方案。然后进行临床前体内研究，比较不同方案在 H1299 异种移植中的肿瘤抑制作用。建立 PK/PD 模型以量化 ER 和 GM 的抗肿瘤相互作用。
当 ER 先于 GM 时观察到协同作用，但其他顺序显示拮抗作用。将最佳的体外方案或间隔方案应用于动物研究，该方案显示出比同时组更大的抗肿瘤效果。PK/PD 模型表明，两种药物的相互作用在同时治疗中是相加的，而在间隔方案中是协同的。模拟结果表明，间隔方案可以延长肿瘤生长的时间，并且如果治疗时间更长，则与同时组相比表现出更明显的抗肿瘤效果。
两种药物的间隔方案可以达到协同的抗肿瘤作用，优于同时治疗。
