Pharmacokinetics and Anti-asthmatic Potential of Non-parenterally Administered Recombinant Human Interleukin-1 Receptor Antagonist in Animal Models
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概要
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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.
- 社団法人 日本薬理学会の論文
- 2006-11-20
著者
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Wang Li
State Key Laboratory Of Natural And Biomimetic Drugs And School Of Pharmaceutical Sciences Peking Un
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Wang Jian-cheng
State Key Laboratory Of Natural And Biomimetic Drugs And School Of Pharmaceutical Sciences Peking Un
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Zhang Qiang
中華人民共和国
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Zhang Q
State Key Laboratory Of Natural And Biomimetic Drugs And School Of Pharmaceutical Sciences Peking Un
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Zhang Q
School Of Pharmaceutical Sciences Peking University
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Han Pu
中華人民共和国
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Han Pu
Beijing Medical University United Biological Engineering Co.
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Zhang Xuan
State Key Laboratory Of Natural And Biomimetic Drugs And School Of Pharmaceutical Sciences Peking Un
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LIU Xiang-Rui
Department of Pharmaceutics, Peking University
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LU Wan-Liang
State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical Sciences, Peking U
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ZHANG Qiang
State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical Sciences, Peking U
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LI Ting
State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical Sciences, Peking U
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HONG Hai-Yan
Beijing Medical University United Biological Engineering Co.
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YAO Yan-Sheng
Beijing Medical University United Biological Engineering Co.
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LI Zhong-Kun
State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical Sciences, Peking U
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WANG Gui-Ling
State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical Sciences, Peking U
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CAO Yi
State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical Sciences, Peking U
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LIU Xiang-Rui
State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical Sciences, Peking U
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Cao Yi
State Key Laboratory Of Natural And Biomimetic Drugs And School Of Pharmaceutical Sciences Peking Un
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Zhang Qiang
State Key Laboratory Of Natural And Biomimetic Drugs And School Of Pharmaceutical Sciences Peking Un
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Zhang X
State Key Laboratory Of Natural And Biomimetic Drugs And School Of Pharmaceutical Sciences Peking Un
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Zhang Xuan
Department Of Pharmaceutics Peking University School Of Pharmaceutical Sciences
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Liu Xiang-rui
Department Of Pharmaceutics Peking University
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Wang Jian-cheng
Department Of Pharmaceutics Peking University
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Lu Wan-liang
中華人民共和国
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Wang Gui-ling
State Key Laboratory Of Natural And Biomimetic Drugs And School Of Pharmaceutical Sciences Peking Un
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Li Zhong-kun
State Key Laboratory Of Natural And Biomimetic Drugs And School Of Pharmaceutical Sciences Peking Un
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Li Ting
State Key Laboratory Of Natural And Biomimetic Drugs And School Of Pharmaceutical Sciences Peking Un
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