Wells P G, Moore G W, Rabin D, Wilkinson G R, Oates J A, Stacpoole P W
Diabetologia. 1980 Aug;19(2):109-13. doi: 10.1007/BF00421855.
Dichloroacetate decreases plasma glucose, lactate, and alanine concentrations in normal and diabetic subjects, and lowers lactate concentrations and increases survival in animals with experimentally induced lactic acidosis. The relationship between these effects and plasma dichloroacetate concentrations have not been previously studied in man. Dichloroacetate (1-50 mg/kg) was infused over 30 min to 16 healthy subjects and plasma drug concentrations were followed by gas chromatography over the next 8 h. Peak plasma concentrations were linearly related to the dose (r = 0.98, p < 0.001) up to 30 mg/kg, above which 4 of 7 subjects had disproportionately high plasma drug concentrations. Nonlinear disposition was also indicated by the convex decreasing plasma elimination curves; levels declining less rapidly initially than later. At plasma concentrations below 10 micrograms/ml, elimination was monoexponential with a half-life of 32 +/- 11 min (mean +/- SD). Plasma drug clearance also decreased with doses greater than 20 mg/kg. Within 2 h of administration of the maximally effective dichloroacetate dose of 35 mg/kg, plasma lactate concentrations fell 75% below baseline and alanine fell 50% below baseline, while blood glucose was unaffected.
二氯乙酸可降低正常受试者和糖尿病患者的血浆葡萄糖、乳酸和丙氨酸浓度，并降低实验性诱导乳酸酸中毒动物的乳酸浓度并提高其存活率。这些作用与血浆二氯乙酸浓度之间的关系此前尚未在人体中进行过研究。将二氯乙酸（1 - 50毫克/千克）在30分钟内输注给16名健康受试者，并在接下来的8小时内通过气相色谱法跟踪血浆药物浓度。血浆峰值浓度与剂量在30毫克/千克以下时呈线性相关（r = 0.98，p < 0.001），高于此剂量时，7名受试者中有4名的血浆药物浓度异常高。血浆消除曲线呈凸形下降也表明存在非线性处置；浓度最初下降速度比后期慢。在血浆浓度低于10微克/毫升时，消除呈单指数形式，半衰期为32 +/- 11分钟（平均值 +/- 标准差）。当剂量大于20毫克/千克时，血浆药物清除率也会降低。在给予最大有效剂量35毫克/千克的二氯乙酸后2小时内，血浆乳酸浓度降至基线以下75%，丙氨酸降至基线以下50%，而血糖未受影响。
