Haemodialysis studies with dichloroacetate

Abstract

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.