外源性谷胱甘肽在大鼠的药代动力学和器官组织分布

PHARMACOKINETICS AND TISSUE DISTRIBUTION OF EXOGENOUSLY ADMINISTERED GLUTATHIONE IN RATS

研究外源给予ＧＳＨ的药动学特性及其是否被器官组织利用。采用反相Ｃ１８－ＯＤＳ柱，荧光检测器，经丹磺酰氯衍化反应后分离和测定大鼠血浆及器官组织ＧＳＨ水平。结果：静注２００ｍｇ／ｋｇ，腹腔注射６００ｍｇ／ｋｇ和１２００ｍｇ／ｋｇＧＳＨ给大鼠后，血药浓度－时间曲线均反映ＧＳＨ大鼠体内过程符合二室模型，其Ｔ１／２α分别为０．０６ｈ（ＩＶ），０．７５ｈ（ＩＰ）和０．２２ｈ（ＩＰ），Ｔ１／２β依次为０．５４、０．６９和０．６３ｈ。ＩＰ两个剂量组的达峰时间均为０．２５ｈ，最大峰浓度分别为０．７３５ｍｍｏｌ／Ｌ和１．４６２ｍｍｏｌ／Ｌ，而其生物利用度分别为４４％及３３％。ＩＰＧＳＨ１２００ｍｇ／ｋｇ后，大鼠脑、肝、肾、肺及卵巢组织中的ＧＳＨ水平均显著升高，在２ｈ后血浆ＧＳＨ降至正常水平时，上述器官组织中的ＧＳＨ仍维持高的水平。结论：结果提示外源性给予ＧＳＨ可有效地提高器官组织的ＧＳＨ。

PURPOSE The cellular level of reduced glutathione (GSH) is important to protect cells against endogenous and exogenous toxins and carcinogens.Thus supplementation of adequate amounts of cellular GSH would be important in the prevention of the“Apoptosis”of malignant cells through antioxidant effect.The purpose of present research was to study the pharmacokinetics and tissue distribution of exogenously administered GSH in order to clear whether exogenously administration can be utilizable.METHODS An HPLC technique was developed to determine GSH in plasma and tissues of normal S-D rats and its iv or ip administration.The assay was accomplished after derivatization of the samples.RESULTS The plasma concentration decay curves either after iv or ip GSH showed 2 compartments characteristics.The respective cmax for 600 mg/kg ip and 1 200 mg/kg ip were 0.735 mmol/L and 1.42 mmol/L with their'F'values of 44% and 33% compared to iv route.The plasma concentration declinec to the preinijection level at 2h post ip,while the tissues content of the assayed organs increased significantly and steadily of very high levels approaching twice to thrice the preinjection level and maintained constant after 2 hours.CONCLUSIONS These results suggested that the level of GSH in these five organs was increased significantly by exogenously administered routd.