Metabolism and excretion of piperonyl butoxide in the rat
Metabolism and excretion of piperonyl butoxide in the rat
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DOI：
10.1080/00498250600856306
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发表时间：
2006-12-01
期刊：
影响因子：
1.8
通讯作者：
Needham, D.
中科院分区：
文献类型：
--
作者：
Byard, J.;Needham, D.
[C-14]-胡椒基丁醚（PBO）以50或500 mg/kg体重的剂量率灌胃给予雄性和雌性大鼠。在所有情况下，放射性迅速排泄，87-99%在0-48 h排泄物中发现，大部分剂量（64.1-85.0%）在粪便中消除。PBO的代谢是复杂的，通过放射性高效液相色谱法（HPLC）观察到超过25个放射性峰。使用HPLC/串联质谱（MS/MS）和核磁共振（NMR），12个尿液代谢产物的结构分配与4加PBO在粪便中。代谢发生在两个位点：亚甲二氧基环，其打开形成儿茶酚，然后可以进行甲基化，以及2-（2-丁氧基乙氧基）乙氧基甲基侧链，其依次氧化为一系列醇和酸。鉴别的代谢产物约占给药剂量的60%。
[C-14]-piperonyl butoxide (PBO) was administered to male and female rats by gavage at a dose rate of 50 or 500mgkg(-1) body weight. In all cases, the radioactivity was rapidly excreted with 87-99% being found in the 0-48-h excreta and the majority of the dose (64.1-85.0%) being eliminated in faeces. The metabolism of PBO was complex with over 25 peaks of radioactivity being seen by radio-high-performance liquid chromatography (HPLC). Using HPLC/tandem mass spectrometry (MS/MS) and nuclear magnetic resonance (NMR), 12 urine metabolites were assigned structures together with four plus PBO in faeces. Metabolism occurred at two sites: the methylenedioxy ring, which opened to form a catechol that could then undergo methylation, and the 2-(2-butoxyethoxy) ethoxymethyl side-chain, which underwent sequential oxidation to a series of alcohols and acids. The identified metabolites accounted for approximately 60% of the administered dose.