Curry S H, Lorenz A, Henderson G N, Mars D R, Stacpoole P W
College of Pharmacy, University of Florida, Gainesville 32610.
Eur J Clin Pharmacol. 1991;40(6):613-7. doi: 10.1007/BF00279980.
Seven patients undergoing routine thrice weekly haemodialysis for endstage renal failure participated in 12 investigations of dichloroacetate (DCA) pharmacokinetics and pharmacodynamics. DCA doses were 50 mg/kg by i.v. infusion over 30 min. In each investigation single doses were administered to each subject on two consecutive days, one being a day during which the patient was dialyzed. The timing of drug administration, relative to dialysis, was varied to assess the effect of dialysis on the apparent volume of distribution and elimination rate constants of DCA and on its effect on blood glucose and lactate. Dialysis increased the clearance of DCA by approximately 60%, but had no effect on its apparent volume of distribution. Dialysis did not reduce the maximal lactate-lowering effect of DCA, but slightly decreased the duration of this effect. Blood glucose levels were not significantly altered by DCA and no adverse drug effects were observed. We conclude that dialysis increases plasma clearance of DCA, but has little influence on the metabolic effects of the drug when given at 50 mg/kg doses. DCA can safely and effectively be given to hemodialysis patients who may require the drug for treatment of lactic acidosis.
7名终末期肾衰竭患者接受每周3次的常规血液透析,参与了12项关于二氯乙酸(DCA)药代动力学和药效学的研究。DCA剂量为50mg/kg,静脉输注30分钟。在每次研究中,每位受试者在连续两天接受单次给药,其中一天为患者进行透析的日子。相对于透析改变给药时间,以评估透析对DCA的表观分布容积和消除速率常数的影响,以及对其血糖和乳酸的影响。透析使DCA的清除率增加约60%,但对其表观分布容积无影响。透析并未降低DCA降低乳酸的最大效应,但略微缩短了该效应的持续时间。DCA未显著改变血糖水平,且未观察到药物不良反应。我们得出结论,透析增加了DCA的血浆清除率,但以50mg/kg剂量给药时对该药物的代谢效应影响很小。对于可能需要该药物治疗乳酸酸中毒的血液透析患者,可以安全有效地给予DCA。