二氯乙酸钠静脉给药在兔体内的药物动力学

Pharmacokinetics of intravenously administered sodium dichloroac-etate in rabbits

作者用反相离子对高效液相色谱法研究二氯乙酸钠（ＤＣＡ－Ｎａ）在兔体内的药物动力学．静脉给药各组的血清中ＤＣＡ－Ｎａ浓度的变化均符合一室开放模型．ｉｖＤＣＡ－Ｎａ１８０ｍｇ／ｋｇ组：Ｔ１／２０．６７ｈ，Ｃｌ０．３１Ｌ／（ｋｇ·ｈ），Ｖｄ０．２８Ｌ／ｋｇ．静脉输注（ｉｎｆ）５０，１００和２００ｍｇ／ｋｇ组间的主要药动学参数无显著差异，均值为Ｔ１／２０．７１，Ｖｄ０．４４Ｌ／ｋｇ，Ｃｌ０．４２Ｌ／（ｋｇ·ｈ）．ｉｎｆ３００ｍｇ／ｋｇ组的Ｔ１／２１．０１ｈ，Ｃｌ０．３０Ｌ／（ｋｇ·ｈ），明显不同于其它ｉｎｆ组，提示ＤＣＡ－Ｎａ可能存在非线性药物动力学．超滤法研究其血清蛋白结合率低于３８％．

Pharmacokinetic study on intravenously administered sodium dichloroacetate(DCA-Na)was car-ried out in rabbits using reversed-phase ion-pair high performance liquid chromatography.The changes inDCA-Na serum concentration of each group were best described as one-compartment open model.In the iv180 mg/kg group,T1/2 was 0.67 h,Cl 0.31 L/(kg·h)and Vd 0.28 L/kg.The main parameters of infusion(inf)50,100 and 200 mg/kg groups showed no significant difference,the mean values being T1/2 0.71 h,Vd0.44 L/kg and Cl 0.42 L/(kg·h).However,in the inf 300 mg/kg group,parameters such as T1/2 1.01 hand Cl 0.30 L/(kg·h) were significantly different from those of other inf groups,suggesting that DCA-Namight have a nonlinear pharmacokinetic process.Serum protein binding rate of DCA-Na measured by ultrafil-tration was lower than 38%.