谷胱甘肽及其构成氨基酸在犬经口、静注给药的药代动力学  

Pharmacokinetics of Glutathione and the Component Amino Acids by Gavage and iv in Beagle Dogs

作　　者：石京山[1] 盛美萍[2] 

机构地区：[1]遵义医学院药理学教研室,遵义563003 [2]上海医科大学基础医学院药理学教研室,上海200032

出　　处：《上海医科大学学报》2000年第1期57-60,共4页Journal of Fudan University(Medical Science)

摘　　要：目的　主要研究谷胱甘肽（ＧＳＨ）口服后的吸收情况。方法　Ｂｅａｇｌｅ犬５只，先后分别经口、静注给予ＧＳＨ及其构成氨基酸后，用ＨＰＬＣ法测定血中浓度。结果　在清醒犬，单剂量（３．８９、１．６２ｍｍｏｌ／ｋｇ）一次或单剂量（０．４９ｍｍｏｌ／ｋｇ）连续５、１０ｄ经口给ＧＳＨ后，犬前肢静脉血浆中ＧＳＨ、甘氨酸明显升高（Ｐ＜０．０５～０．０１）；如上单次给予１．６２ｍｍｏｌ／ｋｇ（等于ＧＳＨ分子中含有的摩尔数）构成氨基酸后，血浆中的ＧＳＨ水平未见变化，但构成氨基酸均显著增加（Ｐ＜０．０１）；在麻醉犬，经口给ＧＳＨ１．６２ｍｍｏｌ／ｋｇ后，１～６ｈ内肠系膜静脉血浆ＧＳＨ水平高于前肢静脉（Ｐ＜０．０５～０．０１）；清醒犬ｉｖＧＳＨ０．０６５ｍｍｏｌ／ｋｇ后静脉血浆中ＧＳＨ的Ｋｅｌ１和Ｔ１／２α分别为８．０４ｈ－１和０．０９ｈ，且在降至基值后又出现一个再分布的小峰。结论　ＧＳＨ经口给药后部分可以整分子吸收，经肝脏后血浆中ＧＳＨ浓度明显下降，可能是由于肝脏的摄取所致。Purpose To study mainly the absorption of glutathione (GSH) after administered by gavage. Methods 5 Beagle dogs were administered GSH and the component amino acids by gavage and iv,respectively.The concentrations of glutathione,glutamate (Glu),cystein (Cys) and glycin (Gly) in plasma were determined by HPLC with a variable wavelength fluorometric detector. Results In un anaesthetic Beagle dogs,a significant increase of GSH and Gly was observed when single dose of GSH was administered by gavage (3.89,1.62 mmol/kg) for 1 day or (0.49 mmol/kg) for 5 days,10 days( P <0.05-0.01).The level of GSH in plasma remained unchanged after giving (by gavage) a mixture of Glu( 1.62 mmol/kg),Cys(1.62 mmol/kg) and Gly(1.62 mmol/kg) although all of them were increased significantly ( P <0.01).During 1-6 h,the content of GSH in plasma in the mesentery vein was higher than that in the forelimb vein after giving single dose of GSH 1.62 mmol/kg ( P <0.05-0.01) in anaesthetic Beagle dogs.The GSH concentrationtime curve in the plasma after iv GSH 0.065 mmol/kg presented bi peak,in which a small peak was observed after the level of GSH decreasing rapidly to physiological basic value.The K el 1 and T 1/2α of the rapid elimination were 8.04 h -1 and 0.09 h,respectively. Results In un anaesthetic Beagle dogs,a significant increase of GSH and Gly was observed when single dose of GSH was administered by gavage (3.89,1.62 mmol/kg) for 1 day or (0.49 mmol/kg) for 5 days,10 days( P <0.05-0.01).The level of GSH in plasma remained unchanged after giving (by gavage) a mixture of Glu( 1.62 mmol/kg),Cys(1.62 mmol/kg) and Gly(1.62 mmol/kg) although all of them were increased significantly ( P <0.01).During 1-6 h,the content of GSH in plasma in the mesentery vein was higher than that in the forelimb vein after giving single dose of GSH 1.62 mmol/kg ( P <0.05-0.01) in anaesthetic Beagle dogs.The GSH concentrationtime curve in the plasma after iv GSH 0.065 mmol/kg presented bi peak,in which a small p

关 键 词：谷胱甘肽 BEAGLE犬 药物代谢动力学 GSH 

分 类 号：R969.1[医药卫生—药理学]