Zileuton

Overview

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. WP

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and extended release formulation of zileuton are still available (Zyflo CR), the 300 mg immediate release tablet was withdrawn from the U.S. market on February 12, 2008.[1][2] WP

Uses, dosage and effects

Treatment

Should an overdose occur, the patient should be treated symptomatically and supportive measures instituted as required. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage; usual precautions should be observed to maintain the airway. A Certified Poison Control Center should be consulted for up-to-date information on management of overdose with Zyflo CR. WP⚠ Wikipedia itself has flagged this text: citation needed.

Risks and side effects

Adverse effects

The most common adverse reactions reported by patients treated with Zyflo CR were sinusitis (6.5%), nausea (5%), and pharyngolaryngeal pain (5%) vs. placebo, 4%, 1.5%, and 4% respectively. WP⚠ Wikipedia itself has flagged this text: citation needed.

Interactions

Drug interactions

Zileuton is a minor substrate of CYP1A2, 2C8/9, 3A4, and a weak inhibitor of CYP 1A2. The drug has been shown to increase the serum concentration or effects of theophylline, propranolol, and warfarin, although significant increase in prothrombin time is not obvious. It is advised that the doses of each medication be monitored and/or reduced accordingly. WP

Other interactions

The avoidance of alcohol is recommended due to increased risk of CNS depression as well as an increased risk of liver toxicity. In addition, the herbal supplement St. John's wort may decrease the serum levels of zileuton.[3] WP

Pharmacology

Pharmacokinetics

Following oral administration zileuton is rapidly absorbed with a mean time to peak blood serum concentration of 1.7 hours and an average half-life elimination of 2.5 hours. Blood plasma concentrations are proportional to dose, whereas the absolute bioavailability is unknown. WP⚠ Wikipedia itself has flagged this text: citation needed.

The apparent volume of distribution of zileuton is approximately 1.2 L/kg. Zileuton is 93% bound to plasma proteins, primarily to albumin, with minor binding to alpha-1-acid glycoprotein. WP⚠ Wikipedia itself has flagged this text: citation needed.

Elimination of zileuton is primarily through metabolites in the urine (~95%) with the feces accounting for the next largest amount (~2%). The drug is metabolized by the cytochrome P450 enzymes: CYP1A2, 2C9, and 3A4.[4] WP

Chemistry

Formula

C11H12N2O2S PC

CAS number

111406-87-2 PC

Molar mass (g/mol)

236.29 PC

IUPAC name (computed by PubChem)

1-[1-(1-benzothiophen-2-yl)ethyl]-1-hydroxyurea PC

SMILES

CC(C1=CC2=CC=CC=C2S1)N(C(=O)N)O PC

InChIKey

MWLSOWXNZPKENC-UHFFFAOYSA-N PC

PubChem CID

60490

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Zileuton (Oral Route)
2. Other Zyflo consumer information
3. Other Zileuton monograph
4. Other Zyflo Drug Information

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.