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学科主题: 药学
题名:
Pharmacokinetics and anti-asthmatic potential of non-parenterally administered recombinant human interleukin-1 receptor antagonist in animal models
作者: Li, Ting; Lu, Wan-Liang; Hong, Hai-Yan; Yao, Yan-Sheng; Han, Pu; Li, Zhong-Kun; Wang, Gui-Ling; Cao, Yi; Liu, Xiang-Rui; Wang, Jian-Cheng; Zhang, Xuan; Zhang, Qiang
关键词: recombinant human interleukin-1 receptor antagonist (rhIL-1ra) ; pharmacokinetics ; asthma ; soluble intercellular cel I adhesion molecule (slCAM-1) ; P-selectin
刊名: JOURNAL OF PHARMACOLOGICAL SCIENCES
发表日期: 2006-11-01
DOI: 10.1254/jphs.FPJ06007X
卷: 102, 期:3, 页:321-330
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: ABSORPTION ENHANCERS ; BRONCHIAL-ASTHMA ; P-SELECTIN ; DISEASE ; DELIVERY ; RATS ; PEPTIDES ; PROTEINS ; ADHESION ; INFLAMMATION
英文摘要:

The objectives of this study were to define the pharmacokinetics of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) and its effects on allergic asthma, cell adhesion molecules, and upper respiratory tract following non-parenteral administration in animals. Pharmacokinetics and immunomodulating effects of rhIL-1ra were investigated in Sprague-Dawley rats and asthmatic guinea pigs, respectively. Effects on the upper respiratory tract following the applications of rhIL-1ra were investigated on the ex vivo nasal mucosa of Sprague-Dawley rats and in situ in the upper palate of Chinese toads. Absolute bioavailabilities after intratracheal and intranasal administrations of rhIL-1ra were 94.3% and 24.8%, respectively. After administration of rhIL-1ra solution as ultrasonic spraying, the asthmatic symptom in guinea pigs was obviously attenuated. The plasma soluble intercellular cell adhesion molecule (sICAM-1) and P-selectin levels in asthmatic guinea pigs were each dose-dependently reduced with the increase of rhIL-1ra dose. The rhIL-1ra solution after administration via the airway seemed to have no impact on the integrity of nasal mucosa and mucocilia clearance in the upper respiratory tract. The present study provides evidence that rhIL-1ra effectively suppresses allergen-induced asthmatic symptoms through spraying, which corresponds to nasal and pulmonary absorption or both, and the efficacy is associated with downregulation of sICAM-1 and P-selectin expressions.

语种: 英语
WOS记录号: WOS:000242328500008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57648
Appears in Collections:北京大学药学院_期刊论文

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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
3.Beijing Med Univ, United Biol Engn Co, Beijing 100083, Peoples R China

Recommended Citation:
Li, Ting,Lu, Wan-Liang,Hong, Hai-Yan,et al. Pharmacokinetics and anti-asthmatic potential of non-parenterally administered recombinant human interleukin-1 receptor antagonist in animal models[J]. JOURNAL OF PHARMACOLOGICAL SCIENCES,2006,102(3):321-330.
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