title: Human kinetics of orally and intravenously administered low-dose 1,2-(13)C-dichloroacetate.
abstract: Dichloroacetate (DCA) is a putative environmental hazard, owing to its ubiquitous presence in the biosphere and its association with animal and human toxicity. We sought to determine the kinetics of environmentally relevant concentrations of 1,2-(13)C-DCA administered to healthy adults. Subjects received an oral or intravenous dose of 2.5 microg/kg of 1,2-(13)C-DCA. Plasma and urine concentrations of 1,2-(13)C-DCA were measured by a modified gas chromatography-tandem mass spectrometry method. 1,2-(13)C-DCA kinetics was determined by modeling using WinNonlin 4.1 software. Plasma concentrations of 1,2-(13)C-DCA peaked 10 minutes and 30 minutes after intravenous or oral administration, respectively. Plasma kinetic parameters varied as a function of dose and duration. Very little unchanged 1,2-(13)C-DCA was excreted in urine. Trace amounts of DCA alter its own kinetics after short-term exposure. These findings have important implications for interpreting the impact of this xenobiotic on human health.
authors.affiliation: General Clinical Research Center, University of Florida, 1600 Archer Road, Gainesville, Florida 32610, USA.
authors.forename: Minghong
authors.initials: M
authors.lastname: Jia
authors.forename: Bonnie
authors.initials: B
authors.lastname: Coats
authors.forename: Monisha
authors.initials: M
authors.lastname: Chadha
authors.forename: Barbara
authors.initials: B
authors.lastname: Frentzen
authors.forename: Javier
authors.initials: J
authors.lastname: Perez-Rodriguez
authors.forename: Paul A
authors.initials: PA
authors.lastname: Chadik
authors.forename: Richard A
authors.initials: RA
authors.lastname: Yost
authors.forename: George N
authors.initials: GN
authors.lastname: Henderson
authors.forename: Peter W
authors.initials: PW
authors.lastname: Stacpoole
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001682:Biological Availability; D002247:Carbon Isotopes; D003999:Dichloroacetic Acid / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000032:analysis*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012984:Software; D013997:Time Factors
chemical_list: D002247:Carbon Isotopes; D003999:Dichloroacetic Acid