YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
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Crush syndromeモデルラットにおけるdexamethasoneの薬物動態の変化と特徴
村田 勇大塚 晃生原 千裕本橋 理沙河野 詩穂井上 裕金本 郁男
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2015 年 135 巻 2 号 p. 315-322

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  Crush syndrome (CS) is characterized by ischemia/reperfusion-induced rhabdomyolysis and subsequent systemic inflammation and has a high mortality rate, even when treated with conventional therapy. In previous studies, we demonstrated that treatment of rats with acute lethal CS using dexamethasone (DEX) had therapeutic effects in laboratory findings and improved the clinical course of CS. However, because the application of DEX in CS therapy is unknown, evaluation of the pharmacokinetic parameters of DEX was considered essential to support its clinical use. Here, we investigated the pharmacokinetic characteristics of DEX in a rat model of CS. Anesthetized rats were subjected to bilateral hind limb compression using rubber tourniquets for 5 h, followed by reperfusion for 0 to 24 h. Rats were divided randomly into 4 groups: saline-treated sham (S) and CS groups and 5.0 mg/kg DEX-treated S (S-DEX) and CS (CS-DEX) groups. Blood and tissue samples were collected for HPLC analysis. In the CS-DEX group, the pharmacokinetic parameters of the area under the concentration-time curve, mean residence time, and distribution volume levels increased significantly compared to the S-DEX group, whereas total body clearance, elimination rate constant, and renal clearance levels decreased significantly. Moreover, decrease of muscle tissue DEX concentration and of CYP3A activity were observed in the CS-DEX group. These results show the pharmacokinetic characteristics of DEX in the rat CS model and support the potential use of DEX in disaster medical care.

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© 2015 by the PHARMACEUTICAL SOCIETY OF JAPAN
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