title: Metabolomic analysis reveals novel isoniazid metabolites and hydrazones in human urine.
abstract: 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.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Miao
authors.forename: Lirong
authors.initials: L
authors.lastname: Zhang
authors.forename: Sarah Ann
authors.initials: SA
authors.lastname: Neuenswander
authors.forename: Justin T
authors.initials: JT
authors.lastname: Douglas
authors.forename: Xiaochao
authors.initials: X
authors.lastname: Ma
mesh_terms: D000328:Adult; D000601:Amino Acids, Essential / Q000378:metabolism; D000995:Antitubercular Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use / Q000652:urine*; D005260:Female; D006801:Humans; D006835:Hydrazones / Q000652:urine*; D006900:Hydroxylation; D007538:Isoniazid / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use / Q000652:urine*; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged
chemical_list: D000601:Amino Acids, Essential; D000995:Antitubercular Agents; D006835:Hydrazones; D007538:Isoniazid