口服还原型谷胱甘肽片在大鼠肝、脑、肾组织中的分布及其药动学

目的探讨口服还原型谷胱甘肽(GSH)片在大鼠肝、脑、肾组织中的分布及其药动学。方法Wistar大鼠84只,随机分为7组,每组12只,6只按120 mg·kg~(-1)灌服GSH片,另6只灌服溶媒,容量0.12 mL·kg~(-1)。分别于给药后0.5、1、2、3、5、8和12 h采集各组动物肝、脑、肾制作组织匀浆,HPLC法测定各组织中的GSH浓度,3p97软件计算药动学参数。结果口服GSH在肝、脑、肾的药-时曲线均为一室摸型;t_(1/2Ka)分别为(1.14±0.08)、(0.75±0.07)和(0.53±0.07)h;t_(1/2Ke)分别为(1.62±0.15)、(1.6±0.7)和(0.9±0.5)h;t_(max)分别为(2.8±0.4)、(2.7±0.6)和(1.2±0.5)h;c_(max)分别为(1 733±341)、(89±11)和(27.2±0.9)μg·g~(-1);AUC_(0～t)分别为(8 480±1 422)、(74.9±0.6)和(51±15)μg·h·g~(-1)。结论口服GSH能达肝、脑、肾组织,其中肝组织浓度较高。

Distribution and pharmacokinetics of oral tablet of reduced glutathione in liver,brain,and kidney of rats

AIM To investigate distribution and pharmacokinetics of oral tablet of reduced glutathione (GSH) in liver,brain,and kidney of rats.METHODS Eighty-four rats were randomly divided into 0.5,1, 2,3,5,8 and 12 h group with 12 rats for each.Six rats in each group were administered oral GSH tablet (all 120 mg·kg~(-1)),and others were solvent control.Tissue homogenate of liver,brain,and kidney of experimental animal was made after administration 0.5,1,2,3,5,8 and 12 h.The concentrations of GSH in liver,brain,and kidney were detected by HPLC method,and pharmacokinetic parameters were calculated with 3p97 software program.RESULTS The GSH concentration curves are presented by one-compartment model. The main pharmacokinetic parameters of liver,brain,and kidney including were:t_(1/2Ka)(1.14±0.08),(0.75±0.07) and(0.53±0.07) h;t~(1/2Ke)(1.62±0.15),(1.6±0.7) and(0.9±0.5) h;t_(max)(2.8±0.4),(2.7±0.6) and(1.2±0.5) h;c_(max)(1 733±341),(89±11) and(27.2±0.9)μg·g~(-1);AUC_(0-1)(8 480±1 422),(74.9±0.6) and(51±15)μg·h·g~(-1),respectively.CONCLUSION GSH may be distributed into rat liver,brain,and kidney after administration oral tablets.The concentration of GSH in liver is the most highest among liver,brain,and kidney.