Premium
Human Kinetics of Orally and Intravenously Administered Low‐Dose 1,2‐ 13 C‐Dichloroacetate
Author(s) -
Jia Minghong,
Coats Bonnie,
Chadha Monisha,
Frentzen Barbara,
PerezRodriguez Javier,
Chadik Paul A.,
Yost Richard A.,
Henderson George N.,
Stacpoole Peter W.
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006292627
Subject(s) - chemistry , urine , kinetics , pharmacology , oral administration , pharmacokinetics , toxicity , chromatography , medicine , biochemistry , physics , organic chemistry , quantum mechanics
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 μg/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.