Metabolomic Analysis Reveals Novel Isoniazid Metabolites and Hydrazones in Human Urine
Metabolomic Analysis Reveals Novel Isoniazid Metabolites and Hydrazones in Human Urine
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DOI：
10.2133/dmpk.dmpk-11-rg-055
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发表时间：
2011-01-01
影响因子：
2.1
通讯作者：
Ma, Xiaochao
中科院分区：
文献类型：
--
作者：
Li, Feng;Miao, Yan;Ma, Xiaochao
异烟肼(INH)是结核病控制的一线药物；INH的副作用被认为与其代谢有关，本研究旨在全面描述异烟肼的代谢。代谢组学策略被用来描述异烟肼在人体内的代谢。在人尿中鉴定出8种已知的异烟肼代谢物和7种新的异烟肼类代谢物。新产品包括两个羟化异烟肼代谢物和五个肼类化合物。两个新的代谢产物被鉴定为2-氧代-1，2-二氢-吡啶-4-碳肼和异烟肼N-氧化物。异烟肼与必需氨基酸代谢的中间体--亮氨酸和/或异亮氨酸、赖氨酸、酪氨酸、色氨酸和苯丙氨酸的缩合反应生成了五个新的肼类化合物。这项研究加深了我们对异烟肼代谢和处置的认识，并可能为研究异烟肼的毒性提供新的途径。
Isoniazid (INH) is a first-line drug for tuberculosis control; the side effects of INH are thought to be associated with its metabolism, and this study was designed to globally characterize isoniazid metabolism. Metabolomic strategies were used to profile isoniazid metabolism in humans. Eight known and seven novel INH metabolites and hydrazones were identified in human urine. The novel products included two hydroxylated INH metabolites and five hydrazones. The two novel metabolites were determined as 2-oxo-1,2-dihydro-pyridine-4-carbohydrazide and isoniazid N-oxide. Five novel hydrazones were produced by condensation of isoniazid with keto acids that are intermediates in the metabolism of essential amino acids, namely, leucine and/or isoleucine, lysine, tyrosine, tryptophan, and phenylalanine. This study enhances our knowledge of isoniazid metabolism and disposition and may offer new avenues for investigating INH-induced toxicity.