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標題: | St. John’s wort與Indinavir於大鼠腸道內藥動學交互作用之研究 A Study on Pharmacokinetic Interactions between St. John’s wort and Indinavir in Rat Small Intestine |
作者: | Ming-Yen Lai 賴明彥 |
指導教授: | 何藴芳(Yunn-Fang Ho) |
共同指導教授: | 余秀瑛(Hsiu-Ying Yu) |
關鍵字: | 藥動學,St. John’s wort,Indinavir,交互作用, Indinavir,St. John’s wort,Pharmacokinetic Interactions, |
出版年 : | 2004 |
學位: | 碩士 |
摘要: | 近年來,St. John’s wort(Hypericum perforatum,SJW)萃取物普遍地被使用於輕度到中度憂鬱症的治療,其主要的活性成份包括hypericin、pseudohypericin及hyperforin等。研究報告顯示,SJW萃取物可能影響P-glycoprotein(Pgp)及Cytochrome P450(CYPs)於大鼠及人體中的活性,進而影響同為CYP3A4 和Pgp受質的HIV蛋白酶抑制劑indinavir之臨床效用。臨床試驗指出,服用SJW會降低indinavir在人體的血中濃度。因此,本研究期望建立一大鼠小腸灌流實驗模式,進一步釐清St. John’s wort與indinavir間之藥品交互作用。 由本實驗之結果可明顯地觀察到,每日餵食雄性Wistar大鼠300 mg的St. John’s wort萃取物連續15天後,在0.05、0.1、0.5及1 mL/min四種不同灌流速度時,小腸中水份的吸收率、水份的淨損量、indinavir的吸收率及indinavir吸收廓清率大部份都明顯降低;而indinavir於肝門靜脈及肝靜脈的血中濃度也明顯降低;大部份的藥品動態學參數亦明顯改變,其差異都具有統計上意義。但是,indinavir的肝臟萃取率及肝臟清除率的差異則不具有統計上意義。 由本實驗之結果推論,St. John’s wort與indinavir間之藥品交互作用中,Pgp及CYPs可能是很重要的影響因子。未來若能進一步研究大鼠小腸或肝臟中CYPs 及Pgp的活性及蛋白質量表現,將有助於釐清本實驗之藥品交互作用的原因。 In recent years, St. John's wort (Hypericum perforatum, SJW) was used as an alternative therapy for the treatment of mild to moderate depression. Several active compounds from SJW have been isolated, including hypericin, pseudohypericin and hyperforin, etc. Besides, SJW may affect the activities of P-glycoprotein (Pgp) and cytochrome P450 (CYPs) in rats and human. In some clinical observations, SJW can reduce the plasma concentrations of indinavir, a HIV protease inhibitor, which is a substrate of CYP3A4 and Pgp. Therefore, a rat small intestine perfusion model was established for the investigation of the drug interactions between SJW and indinavir. In our study, oral administration of 300 mg/day SJW extracts to male Wistar rats for 15 days mostly reduced the water absorption ratio, water net flux, indinavir absorption ratio and indinavir absorption clearance even using four different perfusion flow rates, 0.05, 0.1, 0.5 and 1 mL/min. Besides, the plasma concentrations of indinavir in portal vein and hepatic vein were reduced significantly, and certain pharmacokinetic parameters of indinavir were also changed. However, no significant difference was observed for the mean hepatic extraction ratio (EH) and hepatic clearance (CLH) after SJW pretreatment. It is suggested that the activities of Pgp and CYPs might be involved in the drug interactions between SJW and indinavir. In the further study, the activity and protein expression of CYPs and Pgp in liver or small intestine will be clarified for the investigation of the drug interactions. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/24713 |
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顯示於系所單位: | 藥學系 |
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