Disposition and pharmacodynamics of dichloroacetate (DCA) and oxalate following oral DCA doses

Healthy volunteers received intravenous and/or oral doses of sodium dichloroacetate (DCA) in various single and multiple dose regimens. A crossover bioavailability study proved abortive because second and subsequent doses showed significantly longer terminal elimination half‐lives (means 3·64 h and 9·9 h, respectively) than was the case for initial doses (1·58 h). A parallel bioavailability comparison failed to show that oral doses were significantly different from 100 per cent bioavailability (AUC oral , 604μgh −1 ml −1 ; AUC i.v. , 489μgh −1 ml −1 ). The time required to elapse between individual doses, in order to prevent second doses having relatively long half‐life values, varied in different individuals from 1 week to greater than 3 months. No cardiac or central nervous system effects were recorded by echocardiography and digit symbol substitution tests, respectively. The mean renal clearance of DCA was 42·9 ml h −1 . No differences were observed in DCA kinetics between male and female subjects.