Zileuton Chemical formula
Synonyms: A-64077; Abbott-64077; Zileutón; Zileutonum. (±)-1-(1-Benzo[b]thien-2-ylethyl)N-hydroxyurea.
Cyrillic synonym: Зилейтон.

💊 Chemical information

Chemical formula: C11H12N2O2S = 236.3.
CAS — 111406-87-2.


In US.

USP 31

(Zileuton). A white to off-white powder. Store in airtight containers. Protect from light.

💊 Adverse Effects and Precautions

The most commonly reported adverse effects associated with zileuton treatment are headache, pain including pharyngolaryngeal pain, gastrointestinal disturbances, myalgia, and sinusitis. Hypersensitivity, urticaria, rash, and leucopenia have been reported in a few patients. Zileuton has also been associated with raised liver enzyme values and severe hepatic injury. Zileuton is not suitable for the treatment of acute asthma attacks.

Effects on the liver.

Cases of severe hepatotoxicity including fatalities, jaundice, hyperbilirubinaemia, and raised liver enzymes have been reported in patients taking zileuton. US licensed product information therefore contraindicates the use of zileuton in patients with active liver disease or liver transaminase elevations greater than or equal to three times the upper limit of normal. Caution is required in patients with a history of liver disease or who consume substantial quantities of alcohol. Alanine aminotransferase (ALT) is considered the most sensitive indicator of liver injury due to zileuton. Most rises in ALT concentrations occurred in the first 3 months of zileuton therapy,1 and monitoring is therefore recommended before starting zileuton therapy, once a month for the first 3 months of therapy, every 2 to 3 months for the remainder of the first year of therapy, and periodically thereafter.
1. Watkins PB, et al. Clinical pattern of zileuton-associated liver injury: results of a 12-month study in patients with chronic asthma. Drug Safety 2007; 30: 805–15.

💊 Interactions

Zileuton has been reported to impair the metabolism of some drugs metabolised via hepatic cytochrome P450 enzymes, including propranolol, terfenadine, theophylline, and warfarin.

💊 Pharmacokinetics

Zileuton is reported to be well absorbed from the gastrointestinal tract after oral dosage, with peak plasma concentrations of immediate-release preparations occurring within about 2 hours of a dose. It is about 93% bound to plasma proteins. It is extensively metabolised in the liver by the cytochrome P450 isoenzymes CYP1A2, CYP2C9, and CYP3A4, and excreted in the urine, largely as glucuronide metabolites. The elimination half-life is reported to be about 2.5 hours for the immediate-release preparation and about 3 hours for the controlled-release preparation.
1. Wong SL, et al. The pharmacokinetics of single oral doses of zileuton 200 to 800 mg, its enantiomers, and its metabolites, in normal healthy volunteers. Clin Pharmacokinet 1995; 29 (suppl 2): 9–21
2. Awni WM, et al. Pharmacokinetics and pharmacodynamics of zileuton after oral administration of single and multiple dose regimens of zileuton 600 mg in healthy volunteers. Clin Pharmacokinet 1995; 29 (suppl 2): 22–33
3. Braeckman RA, et al. The pharmacokinetics of zileuton in healthy young and elderly volunteers. Clin Pharmacokinet 1995; 29 (suppl 2): 42–8
4. Awni WM, et al. Population pharmacokinetics of zileuton, a selective 5-lipoxygenase inhibitor, in patients with rheumatoid arthritis. Eur J Clin Pharmacol 1995; 48: 155–60
5. Awni WM, et al. The effect of mild or moderate hepatic impairment (cirrhosis) on the pharmacokinetics of zileuton. Clin Pharmacokinet 1995; 29 (suppl 2): 49–61
6. Awni WM, et al. Pharmacokinetics of zileuton and its metabolites in patients with renal impairment. J Clin Pharmacol 1997; 37: 395–404
7. Dubé LM, et al. Zileuton, a leukotriene synthesis inhibitor in the management of chronic asthma: clinical pharmacokinetics and safety. Clin Rev Allergy Immunol 1999; 17: 213–21.

💊 Uses and Administration

Zileuton is an orally active 5-lipoxygenase inhibitor and therefore inhibits leukotriene formation. It is used in the management of chronic asthma (see below) but has no bronchodilator properties and is not suitable for the management of acute attacks. Zileuton is given in oral doses of 600 mg 4 times daily as an immediate-release preparation. A controlled-release formulation of zileuton is also available; the usual oral dose is 1.2 g twice daily. It has also been tried in other disorders including arthritis, allergic rhinitis, and inflammatory bowel disease.


Zileuton has been found to be of some benefit in asthma, including that provoked by cold air, exercise, and NSAIDs. US guidelines for the management of asthma permit its use in addition to inhaled corticosteroid therapy in moderate persistent asthma. Combination of anti-leukotriene drugs with inhaled corticosteroids alone seems however to be less effective than a combination of the latter with long-acting inhaled beta2agonists. Due to a lack of data on efficacy and the need for liver function monitoring, zileuton is also considered a less desirable treatment option for addition to inhaled corticosteroids than the leukotriene receptor antagonists. An intravenous form of zileuton is under investigation for use in asthma.
1. Israel E, et al. The effects of a 5-lipoxygenase inhibitor on asthma induced by cold, dry air. N Engl J Med 1990; 323: 1740–4
2. Israel E, et al. The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma. Ann Intern Med 1993; 119: 1059–66
3. McGill KA, Busse WW. Zileuton. Lancet 1996; 348: 519–24
4. Israel E, et al. Effect of treatment with zileuton, a 5-lipoxygenase inhibitor, in patients with asthma: a randomized controlled trial. JAMA 1996; 275: 931–6
5. O’Connor BJ, et al. Zileuton added to low-dose inhaled beclomethasone for the treatment of moderate to severe persistent asthma. Respir Med 2007; 101: 1088–96.

Inflammatory bowel disease.

Despite initial hopes that inhibition of lipoxygenase might prove of benefit in patients with ulcerative colitis,1 a study in those with mild or moderately active relapsing disease found that the symptomatic benefits of zileuton were confined to those not already receiving sulfasalazine.2 A subsequent study showed zileuton was not significantly better than placebo in maintaining remission.3 For a discussion of inflammatory bowel disease and its management.
1. Laursen LS, et al. Selective 5-lipoxygenase inhibition in ulcerative colitis. Lancet 1990; 335: 683–5
2. Laursen LS, et al. Selective 5-lipoxygenase inhibition by zileuton in the treatment of relapsing ulcerative colitis: a randomized double-blind placebo-controlled multicentre trial. Eur J Gastroenterol Hepatol 1994; 6: 209–15
3. Hawkey CJ, et al. A trial of zileuton versus mesalazine or placebo in the maintenance of remission of ulcerative colitis. Gastroenterology 1997; 112: 718–24.


A study in 8 patients with allergic rhinitis found that a single dose of zileuton 800 mg reduced the response to a nasal antigen challenge 3 hours later,1 including reduced sneezing and nasal congestion.
1. Knapp HR. Reduced allergen-induced nasal congestion and leukotriene synthesis with an orally active 5-lipoxygenase inhibitor. N Engl J Med 1990; 323: 1745–8.

💊 Preparations

Proprietary Preparations

USA: Zyflo.
Published October 07, 2018.