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学科主题药学
Preclinical Pharmacokinetic/Pharmacodynamic Models to Predict Schedule-Dependent Interaction Between Erlotinib and Gemcitabine
Li, Mengyao2; Li, Hanqing2; Cheng, Xiaoliang2; Wang, Xipei2; Li, Liang1,2; Zhou, Tianyan1,2; Lu, Wei1,2
关键词Combination Erlotinib Gemcitabine Interval Schedule Pk/pd Model
刊名PHARMACEUTICAL RESEARCH
2013-05-01
DOI10.1007/s11095-013-0978-7
30期:5页:1400-1408
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
资助者Ministry of Science and Technology of the People&prime ; s Republic of China Grant ; National Natural Science Foundation of China (NSFC) Grant ; Ministry of Science and Technology of the People&prime ; s Republic of China Grant ; National Natural Science Foundation of China (NSFC) Grant
研究领域[WOS]Chemistry ; Pharmacology & Pharmacy
关键词[WOS]CELL LUNG-CANCER ; XENOGRAFT MODELS ; PHASE-III ; GROWTH ; TRIAL ; PHARMACOKINETICS ; COMBINATION ; INHIBITOR ; PHARMACODYNAMICS ; CYTOTOXICITY
英文摘要

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.

语种英语
所属项目编号2009ZX09301-010 ; 81273583
资助者Ministry of Science and Technology of the People&prime ; s Republic of China Grant ; National Natural Science Foundation of China (NSFC) Grant ; Ministry of Science and Technology of the People&prime ; s Republic of China Grant ; National Natural Science Foundation of China (NSFC) Grant
WOS记录号WOS:000317348000016
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53775
专题北京大学药学院_药剂学系
作者单位1.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Li, Mengyao,Li, Hanqing,Cheng, Xiaoliang,et al. Preclinical Pharmacokinetic/Pharmacodynamic Models to Predict Schedule-Dependent Interaction Between Erlotinib and Gemcitabine[J]. PHARMACEUTICAL RESEARCH,2013,30(5):1400-1408.
APA Li, Mengyao.,Li, Hanqing.,Cheng, Xiaoliang.,Wang, Xipei.,Li, Liang.,...&Lu, Wei.(2013).Preclinical Pharmacokinetic/Pharmacodynamic Models to Predict Schedule-Dependent Interaction Between Erlotinib and Gemcitabine.PHARMACEUTICAL RESEARCH,30(5),1400-1408.
MLA Li, Mengyao,et al."Preclinical Pharmacokinetic/Pharmacodynamic Models to Predict Schedule-Dependent Interaction Between Erlotinib and Gemcitabine".PHARMACEUTICAL RESEARCH 30.5(2013):1400-1408.
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