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 (AUCoral, 604 micrograms h-1 ml-1; AUCi.v., 489 micrograms h-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.
Curry
S H
SH
College of Pharmacy, University of Florida, Gainesville 32610.
Lorenz
A
A
Chu
P I
PI
Limacher
M
M
Stacpoole
P W
PW
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D001711:Biotransformation; D015924:Blood Pressure Monitors; D003999:Dichloroacetic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004452:Echocardiography / Q000187:drug effects; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010070:Oxalates / Q000493:pharmacokinetics*; D012737:Sex Factors
D010070:Oxalates; D003999:Dichloroacetic Acid