Zileuton

Zileuton

Clinical data
Trade names	Zyflo
AHFS/Drugs.com	Monograph
MedlinePlus	a697013
License data	US FDA: Zileuton
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	Oral
ATC code	none
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	Not yet established
Protein binding	93%
Metabolism	Hepatic (CYP1A2, CYP2C9 and CYP3A4-mediated)
Biological half-life	2.5 hours
Excretion	Renal
Identifiers
IUPAC name N-​[1-​(1-​benzothien-​2-​yl)​ethyl]-​N-​hydroxyurea
CAS Number	111406-87-2 Y
PubChem CID	60490
IUPHAR/BPS	5297
DrugBank	DB00744 Y
ChemSpider	54531 Y
UNII	V1L22WVE2S
KEGG	D00414 Y
ChEBI	CHEBI:10112 Y
ChEMBL	CHEMBL93 Y
ECHA InfoCard	100.121.111
Chemical and physical data
Formula	C11H12N2O2S
Molar mass	236.291 g/mol
3D model (Jmol)	Interactive image
Chirality	Racemic mixture
SMILES O=C(N)N(O)C(c2sc1ccccc1c2)C
InChI InChI=1S/C11H12N2O2S/c1-7(13(15)11(12)14)10-6-8-4-2-3-5-9(8)16-10/h2-7,15H,1H3,(H2,12,14) Y Key:MWLSOWXNZPKENC-UHFFFAOYSA-N Y

Zileuton (trade name ZYFLO) is an orally active inhibitor of 5-lipoxygenase, and thus inhibits leukotrienes (LTB₄, LTC₄, LTD₄, and LTE₄) formation, used for the maintenance treatment of asthma. Zileuton was introduced in 1996 by Abbott Laboratories and is now marketed in two formulations by Cornerstone Therapeutics Inc. under the brand names ZYFLO and ZYFLO CR. The original immediate-release formulation, ZYFLO, is taken four times per day. The extended-release formulation, ZYFLO CR, is taken twice daily.

Although the 600 mg immediate release tablet (Zyflo) and extended release formulation of zileuton are still available (Zyflo CR), the 300 mg immediate release tablet was withdrawn from the U.S. market on February 12, 2008.

Zileuton is indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. Zileuton is not indicated for use in the reversal of bronchospasm in acute asthma attacks. Therapy with zileuton can be continued during acute exacerbations of asthma.

The recommended dose of ZYFLO is one 600 mg tablet, four times per day. The tablets may be split in half to make them easier to swallow. The recommended dose of ZYFLO CR is two 600 mg extended-release tablets twice daily, within one hour after morning and evening meals, for a daily dose of 2400 mg. Do not split ZYFLO CR tablets in half.

Related compounds include montelukast (Singulair) and zafirlukast (Accolate). These two compounds are leukotriene receptor antagonists which block the action of specific leukotrienes, while zileuton inhibits leukotriene formation.

Research on mice suggests that Zileuton used alone or in combination with imatinib may inhibit chronic myeloid leukemia (CML).

The most serious side effect of ZYFLO and ZYFLO CR is a potential elevation of liver enzymes (in 2% of patients). Therefore, zileuton is contraindicated in patients with active liver disease or persistent hepatic function enzymes elevations greater than three times the upper limit of normal. Hepatic function should be assessed prior to initiating ZYFLO CR, monthly for the first 3 months, every 2–3 months for the remainder of the first year, and periodically thereafter.

Neuropsychiatric events, including sleep disorders and behavioral changes, may occur with ZYFLO and ZYFLO CR. Patients should be instructed to notify their healthcare provider if neuropsychiatric events occur while using ZYFLO or ZYFLO CR.