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Xenobiotica
the fate of foreign compounds in biological systems
Volume 34, 2004 - Issue 6
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Research Article

Pharmacokinetics of two major hydroxylated polychlorinated biphenyl metabolites with specific retention in rat blood

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Pages 581-589 | Received 20 Feb 2004, Published online: 22 Sep 2008
 

Abstract

1. Hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) are, depending on their structure, strongly retained in mammalian, fish and bird blood. This is due to strong, though reversible, binding to the thyroxine binding and transporting protein transthyretin. 2,3,3′,4′,5-Pentachloro-4-biphenylol (4-OH-CB 107) and 2,2′,3,4′,5,5′,6-heptachloro-4-biphenylol (4-OH-CB 187) are two of five major OH-PCB congeners in human plasma.

2. The relative amounts of OH-PCB congeners vary between species and also between human populations, in spite of similar PCB congener patterns, and may depend on different pharmacokinetic parameters of the OH-PCBs. In the present study, the pharmacokinetic parameters of 4-OH-CB 107 and 4-OH-CB 187 were determined in the rat after a single intravenous dose of 1 µmol kg−1. Plasma samples were analysed by gas chromatography/mass spectrometry.

3. 4-OH-CB 107 had a half-life of 3.8 days; 4-OH-CB 187 had a half-life of 15 days. Volumes of distribution were 0.07 and 0.11 l kg−1, respectively; clearances (ml h−1) were 0.67 and 0.22, respectively; and the areas under the curve were estimated as approximately 1500 and 4450 nmol h ml−1.

4. The pharmacokinetic parameters thus determined help to explain the observed differences in the relative amounts of OH-PCBs in humans and other mammals exposed to environmental PCBs.

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