二氯乙酸钠药物动力学的统计矩分析

Statistical moment studyon pharmacokinetics of sodium dicmoroac-etate

二氯乙酸钠（ＤＣＡ－Ｎａ）为乳酸脱氢酶激活剂，用于代谢性乳酸酸中毒的治疗。作者用反相离子对高效液相色谱法检测血清中ＤＣＡ－Ｎａ的浓度，并用统计矩法分析ＤＣＡ－Ｎａ在兔体内的药物动力学。结果表明：ｉｖＤＣＡ－Ｎａ１８０ｍｇ／ｋｇ时，药时曲线下面积（ＡＵＣ）为６０５．１（μｇ·ｈ）／ｍｌ，平均驻留时间（ＭＲＴ）为０．８７ｈ，清除率（Ｃｌ）为０．２９Ｌ／（ｋｇ·ｈ），根据稳态血药浓度求得的表现分布容积（Ｖｓｓ）为０．２６Ｌ／ｋｇ；静脉输注（ｉｎｆ）３００ｍｇ／ｋｇ时，ＡＵＣ为６８５．１（μｇ·ｈ）／ｍｌ，ＭＲＴ为２．１３ｈ，Ｃｌ为０．４９Ｌ／（ｋｇ·ｈ），Ｖｓｓ为０．９７／ｋｇ，与ｉｎｆ低剂量组５０，１００和２００ｍｇ／ｋｇ相比，ＭＲＴ明显延长，Ｖｓｓ显著增大。提示：随着剂量的增加，ＤＣＡ－Ｎａ在兔体内可能存在非线性药物动力学，并在某些器官组织中明显浓集。

The serum concentrations of intravenously administrated sodium dichloroacetate ( DCA-Na)were assayed using reversed-phase ion-pair high performance chromatography and study on the pharmacokinetics of intravenously administered DCA-Na in rabbits was carried out by statistical moment analvsis. The resultsshowed that in the case of iv 180 mg/kg,area under the curve(AUC)was 605.10μg·h/ml ,mean residence time (MRT) 0.87 h, clearance(Cl)0.29 L/(kg·h)and apparent volume of distribution obtained from steady state concentration(Vss) 26 L/kg.When intravenous infusion(inf) was that of 300 mg/kg :AUC was 685. 1μ·h /ml,MRT 2.13 h,Cl 0. 49 L/(kg·h) and Vss 0. 97 L/kg,MRT and Vss were significant-ly different from those of inf 50, 100 and 200 mg/kg groups.It is suggested that with the increase of the dosage DCA-Na might have a nonlinear pharmacokinetic process and concentrate in some tissues.