Metabolomic analysis reveals novel isoniazid metabolites and hydrazones in human urine

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Amino Acids, Essential / metabolism
  • Antitubercular Agents / adverse effects
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / therapeutic use
  • Antitubercular Agents / urine*
  • Female
  • Humans
  • Hydrazones / urine*
  • Hydroxylation
  • Isoniazid / adverse effects
  • Isoniazid / metabolism
  • Isoniazid / therapeutic use
  • Isoniazid / urine*
  • Male
  • Metabolome
  • Metabolomics / methods
  • Middle Aged


  • Amino Acids, Essential
  • Antitubercular Agents
  • Hydrazones
  • Isoniazid