Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, USA.
Drug Metab Pharmacokinet. 2011;26(6):569-76. doi: 10.2133/dmpk.DMPK-11-RG-055. Epub 2011 Aug 16.
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.
异烟肼（INH）是结核病控制的一线药物；人们认为 INH 的副作用与其代谢有关，本研究旨在全面描述异烟肼的代谢。采用代谢组学策略来分析人体中的异烟肼代谢。在人尿液中鉴定出了 8 种已知和 7 种新型 INH 代谢物和腙。新型产物包括两种羟基化的 INH 代谢物和 5 种腙。这两种新型代谢物被确定为 2-氧代-1,2-二氢吡啶-4-甲酰肼和异烟肼 N-氧化物。5 种新型腙是由异烟肼与酮酸缩合而成，酮酸是必需氨基酸代谢的中间产物，即亮氨酸和/或异亮氨酸、赖氨酸、酪氨酸、色氨酸和苯丙氨酸。本研究增强了我们对异烟肼代谢和处置的认识，可能为研究 INH 诱导的毒性提供新途径。
