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学科主题: 药学
题名:
Preclinical Pharmacokinetic/Pharmacodynamic Models to Predict Schedule-Dependent Interaction Between Erlotinib and Gemcitabine
作者: 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
发表日期: 2013-05-01
DOI: 10.1007/s11095-013-0978-7
卷: 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
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
项目资助者: Ministry of Science and Technology of the People&prime ; s Republic of China Grant ; National Natural Science Foundation of China (NSFC) Grant
WOS记录号: WOS:000317348000016
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53775
Appears in Collections:北京大学药学院_药剂学系_期刊论文

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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

Recommended Citation:
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.
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