Zileuton: the first 5-lipoxygenase inhibitor for the treatment of asthma

Ann Pharmacother. 1996 Jul-Aug;30(7-8):858-64. doi: 10.1177/106002809603000725.


Objective: To introduce and review zileuton, an orally active 5-lipoxygenase inhibitor that represents the first of a new class of medications to be used in the treatment of asthma.

Data sources: A MEDLINE search (from 1966 to December 1995) was performed to identify pertinent English-language literature.

Study selection: Basic science studies on the pharmacokinetics of zileuton, its pathophysiologic effects on asthma, and clinical efficacy trials were reviewed.

Data extraction: Clinical trials were emphasized. Studies from ex vivo or animal models of pharmacologic and pharmacodynamic effects were considered for review where no in vivo human data were available.

Data synthesis: Zileuton has shown the ability to attenuate induced bronchospasm, produce some degree of bronchodilation, and provide antiinflammatory or steroid-sparing effects with both single doses (800 mg) and chronic treatment (400 and 600 mg qid). Zileuton has been studied in patients requiring daily inhaled beta-adrenergic agonist treatment; however, data from pediatric populations and comparisons with other asthma medications are limited at this time. Adverse effects include dyspepsia and elevated liver enzymes (incidence approximately 3%). One case of jaundice has been reported among the more than 5000 patients treated with zileuton. There is also some concern for drug interactions with hepatically cleared medications, such as theophylline.

Conclusions: Zileuton represents the first drug of a new treatment category for asthma, the 5-lipoxygenase inhibitors. Some people with asthma may receive considerable benefit, but as it is an entirely new drug entity, zileuton's final place in the hierarchy of asthma medications remains to be determined.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Asthma / blood
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchodilator Agents / therapeutic use*
  • Clinical Trials as Topic
  • Drug Interactions
  • Humans
  • Hydroxyurea / adverse effects
  • Hydroxyurea / analogs & derivatives*
  • Hydroxyurea / pharmacology
  • Hydroxyurea / therapeutic use
  • Lipoxygenase Inhibitors / therapeutic use*
  • Theophylline / therapeutic use


  • Anti-Inflammatory Agents, Non-Steroidal
  • Bronchodilator Agents
  • Lipoxygenase Inhibitors
  • Theophylline
  • zileuton
  • Hydroxyurea