PHARMACOKINETICS OF DICHLOROACETATE IN ADULT PATIENTS WITH LACTIC-ACIDOSIS

The pharmacokinetic properties of the lactate-lowering drug dichloroac etate were investigated in 111 adult patients with lactic acidosis who were randomized to receive dichloroacetate as part of a placebo-contr olled clinical trial. The clinical symptoms and etiology of lactic aci dosis varied markedly among patients. Dichloroacetate, at a dose of 50 mg per kilogram of body weight, was administered in a 30-minute intra venous infusion into a peripheral vein. A second dose, identical 50 th e first, was administered 2 hours after beginning the first infusion. Plasma levels of dichloroacetate were determined from blood samples co llected periodically up to 288 hours after administration and the data were subjected to pharmacokinetic modeling. The pharmacokinetic prope rties of dichloroacetate in these acutely ill patients were complex an d differed markedly from those in healthy volunteers, whose data fitte d a one-compartment pharmacokinetic model. In contrast, the data from patients fitted one-, two-, or three-compartment pharmacokinetic model s or even none of these, depending on the individual. Drug clearance i n plasma tended to decrease as the number of compartments required to fit the data increased or as the number of drug treatments increased.