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PHARMACOKINETICS

Human Kinetics of Orally and Intravenously Administered Low-Dose 1,2-13C-Dichloroacetate

Minghong Jia, PhD, Bonnie Coats, ARNP, Monisha Chadha, MD, Barbara Frentzen, ARNP, Javier Perez-Rodriguez, Paul A. Chadik, PhD, Richard A. Yost, PhD, George N. Henderson, PhD and Peter W. Stacpoole, PhD, MD

From the General Clinical Research Center (Dr Jia, Ms Frentzen, Dr Henderson, Dr Stacpoole), Departments of Medicine (Ms Coats, Dr Chadha, Mr Perez-Rodriguez, Dr Henderson, Dr Stacpoole), Biochemistry and Molecular Biology (Dr Stacpoole), Environmental Engineering Sciences (Dr Chadik), and Chemistry (Dr Yost), University of Florida, Gainesville, Florida.

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 1,2-13C-DCA administered to healthy adults. Subjects received an oral or intravenous dose of 2.5 µg/kg of 1,2-13C-DCA. Plasma and urine concentrations of 1,2-13C-DCA were measured by a modified gas chromatography-tandem mass spectrometry method. 1,2-13C-DCA kinetics was determined by modeling using WinNonlin 4.1 software. Plasma concentrations of 1,2-13C-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 1,2-13C-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.

Key Words: Dichloroacetate • pharmacokinetics • environmental toxicology • disinfection by-products

Address for reprints: Peter W. Stacpoole, PhD, MD, General Clinical Research Center, M2-236, University of Florida, 1600 Archer Road, Gainesville, Florida 32610; e-mail: stacpool{at}gcrc.ufl.edu.




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 J. Pharmacol. Exp. Ther.Home page
A. L. Shroads, X. Guo, V. Dixit, H.-P. Liu, M. O. James, and P. W. Stacpoole
Age-Dependent Kinetics and Metabolism of Dichloroacetate: Possible Relevance to Toxicity
J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 1163 - 1171.
[Abstract] [Full Text] [PDF]


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