Biological disposition of sodium dichloroacetate in animals and humans after intravenous administration.

Sodium dichloroacetate, a potential antidote for lactic acidosis, was administered intravenously to rats, dogs, and four humans. In three rats, maximum plasma sodium dichloroacetate concentrations were 120-164 microgram/ml after a 100-mg/kg dose and declined with half-lives of 2.1-4.4 hr. In two dogs, maximal concentrations of 447 and 508 microgram/ml were attained after a 100-mg/kg dose. The subsequent decline was relatively slow with approximate half-lives of 17.1 and 24.6 hr. An intravenous infusion of 10 mg/kg was administered over 20 min to two human subjects. Two other subjects received 20 mg/kg. After the infusion, maximum plasma concentrations of 19.9 and 24.7 microgram/ml were seen with the lower dose and 57.3 and 74.9 microgram/ml were achieved with the higher dose. Thereafter, concentrations declined rapidly with half-lives of 20-36 min. The observed large interspecies differences in half-lives could be explained in terms of differences in the apparent volume of distribution and/or clearance.