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Pulmonary gemcitabine delivery for treating lung cancer: pharmacokinetics and acute lung injury aspects in animals
Min, Rui1; Li, Ting1; Du, Ju1; Zhang, Yan1; Guo, Jia1; Lu, Wan-Liang1
关键词gemcitabine pulmonary delivery lung cancer pharmacokinetics acute lung injury
刊名CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
2008-05-01
DOI10.1139/Y08-039
86期:5页:288-298
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy ; Physiology
研究领域[WOS]Pharmacology & Pharmacy ; Physiology
关键词[WOS]INDUCED NEUTROPHIL CHEMOATTRACTANT ; RESPIRATORY-DISTRESS-SYNDROME ; PHASE-II ; IN-VITRO ; DRUG-DELIVERY ; ABSORPTION ; RATS ; LIPOPOLYSACCHARIDE ; CHEMOTHERAPY ; VINORELBINE
英文摘要

Gemcitabine, a nucleoside analogue for treating lung cancer, is clinically administered as an intravenous infusion. To achieve better patient compliance and more direct effect on the lung, we explored a new gemcitabine pulmonary delivery route and evaluated the pharmacokinetics and acute lung injury aspects in animals. Pharmacokinetics of gemcitabine were measured in Sprague-Dawley rats after intravenous (i.v.), intratracheal instillation by tracheotomy (i.t.t.), intratracheal instillation via orotrachea (i.t.o.), and intragastric (i.g.) administration of gemcitabine. Acute lung injury effects of the pulmonary delivery of gemcitabine were performed in Sprague-Dawley rats after i.t.o. and i.v. administration of gemcitabine and i.t.o. administration of lipopolysaccharide (LPS) as a positive control and physiological saline as a blank control. Indicators for acute lung injury that were evaluated included lung morphology, lung histopathology, lung coefficient, lung wet/dry weight ratio, total cell and classification counts in bronchoalveolar lavage cells (BALC), and total protein and TNF-alpha levels in bronchoalveolar lavage fluids (BALF). After i.t.t. or i.t.o. administration, gemcitabine was quickly absorbed, but i.g. administration led to an undetectable plasma gemcitabine concentration. Absolute bioavailability of gemcitabine after i.t.t. and i.t.o. administration was 91% and 65%, respectively. Gemcitabine given as i.t.o. administration did not cause any overt acute lung injury. All indicators for acute lung injury in the i.t.o. group were similar to those in the i.v. group or in the blank control, but significantly different from those in the positive control. In conclusion, the pharmacokinetics and acute lung injury studies suggest that pulmonary gemcitabine delivery would be a new and promising administration route.

语种英语
WOS记录号WOS:000256626200009
引用统计
被引频次:7[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/400002259/59221
专题北京大学药学院
作者单位1.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100083, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Beijing 100083, Peoples R China
推荐引用方式
GB/T 7714
Min, Rui,Li, Ting,Du, Ju,et al. Pulmonary gemcitabine delivery for treating lung cancer: pharmacokinetics and acute lung injury aspects in animals[J]. CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY,2008,86(5):288-298.
APA Min, Rui,Li, Ting,Du, Ju,Zhang, Yan,Guo, Jia,&Lu, Wan-Liang.(2008).Pulmonary gemcitabine delivery for treating lung cancer: pharmacokinetics and acute lung injury aspects in animals.CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY,86(5),288-298.
MLA Min, Rui,et al."Pulmonary gemcitabine delivery for treating lung cancer: pharmacokinetics and acute lung injury aspects in animals".CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 86.5(2008):288-298.
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