期刊
JOURNAL OF CLINICAL PHARMACOLOGY
卷 46, 期 12, 页码 1449-1459出版社
WILEY
DOI: 10.1177/0091270006292627
关键词
dichloroacetate; pharmacokinetics; environmental toxicology; disinfection by-products
资金
- NCRR NIH HHS [M01 RR000082] Funding Source: Medline
- NIEHS NIH HHS [R01 ES07355, P42 ES07375] Funding Source: Medline
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-C-13-DCA administered to healthy adults. Subjects received an oral or intravenous dose of 2.5 mu g/kg of 1,2-C-13-DCA. Plasma and urine concentrations of 1,2-(13)CDGA were measured by a modified gas chromatographytandem mass spectrometry method. 1,2-(13)G-DCA kinetics was determined by modeling using WinNonlin 4.1 software. Plasma concentrations of 1,2-C-13-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-C-13-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.
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