Pharmacokinetics of two major hydroxylated polychlorinated biphenyl metabolites with specific retention in rat blood
Pharmacokinetics of two major hydroxylated polychlorinated biphenyl metabolites with specific retention in rat blood
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DOI：
10.1080/00498250410001713078
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发表时间：
2004-06-01
期刊：
影响因子：
1.8
通讯作者：
Wehler, EK
中科院分区：
文献类型：
--
作者：
Malmberg, T;Hoogstraate, J;Wehler, EK
1.多氯联苯的羟化代谢物(OH-PCbs)根据其结构，在哺乳动物、鱼类和鸟类的血液中保留很强。这是由于与甲状腺激素结合和运输蛋白甲状腺激素的结合很强，虽然是可逆的。2，3，3‘，4’，5-五氯-4-联苯(4-OH-CB 107)和2，2‘，3，4’，5，5‘，6-七氯-4-联苯(4-OH-CB 187)是人体血浆中五种主要的羟基多氯联苯中的两种。尽管有相似的多氯联苯同系物模式，但羟基多氯联苯的相对量在物种之间和人类种群之间也是不同的，并且可能取决于羟基多氯联苯的不同药代动力学参数。本文测定了4-羟基-CB_(107)和4-羟基-CB_(187)在大鼠体内单次静脉注射1momoL·kg~(-1)后的药代动力学参数。血浆样品用气相色谱/质谱仪进行分析。4-羟基-CB 107的半衰期为3.8天，4-羟基-CB 187的半衰期为15天。分布体积分别为0.07和0.11 L kg(-1)，间隙(mlh(-1))分别为0.67和0.22，曲线下面积估计约为1500和4450nmolhml(-1)。由此确定的药代动力学参数有助于解释在暴露于环境多氯联苯的人类和其他哺乳动物体内观察到的羟基多氯联苯相对量的差异。
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 mumol 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.