Zileuton

236.29

236.29

1308068-626-2

759277|730712

DTXSID9023752

2934990002

94.8

1.6

white to off-white

1.401±0.06 g/cm3(Predicted)

157-158 °C

449.4±47.0 °C(Predicted)

225.6±29.3 °C

1.704

H2O: Practically insoluble (0.5 mg/ml);DMSO: ≥20mg/mL at ~60°C (warm up to 60 C for 5min)

Store at +4°C

7.29E-09mmHg at 25°C

NONH for all modes of transport

1

22-36

26

Xn

P305 + P351 + P338

H302-H319

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P280, P301+P312, P305+P351+P338, P330, P337+P313, and P501|Aggregated GHS information provided by 41 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Minimum oral lethal dose of zileuton in various preparations was 500-4000 mg/kg in mice and 300-1000 mg/kg in rats (providing greater than 3 and 9 times the systemic exposure [AUC] achieved at the maximum recommended human daily oral dose, respectively).

In premarketing studies, zileuton therapy was found to be associated with mild-to-moderate serum aminotransferase elevations. In large prospective studies, ALT elevations above 3 times the upper limit of the normal range occurred in 1.9% of patients treated with zileuton for at least one year, compared to 0.2% of placebo recipients. These elevations were usually transient, asymptomatic and rapidly reversible. However, some patients with ALT elevations reported symptoms suggestive of hepatic injury (fatigue, nausea, abdominal pain) and individual cases of clinically apparent, frank liver injury with jaundice were seen. The typical onset of liver enzyme elevations was within 4 to 8 weeks of starting zileuton, but cases arising after 6 months were also reported. In cases with jaundice, the pattern of serum enzyme elevations was hepatocellular. Immunoallergic and autoimmune features were not prominent. Recovery was rapid, usually within 1 to 2 months. Overall, however, only isolated cases of zileuton related liver injury with jaundice have been reported, and clinically apparent hepatotoxicity from it must be very rare. Results of rechallenge have not been reported. Because of the frequency of serum enzyme elevations during zileuton therapy, monitoring of serum aminotransferase levels is recommended and its use is considered contraindicated in patients with active liver disease. The lack of published reports of zileuton hepatotoxicity may be due to active monitoring for liver test abnormalities and prompt discontinuation if they persist or continue to rise. In addition, zileuton has not been as widely used clinically as montelukast or zafirlukast.

93% bound to plasma proteins, primarily to albumin.

For the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older.|FDA Label

Zileuton is an antiinflammatory leukotriene pathway inhibitor classified as an inhibitor of the enzyme 5-lipoxygenase that is used in the treatment of asthma and allergic rhinitis. Zileuton has been linked to rare cases of drug induced liver disease and is considered to be contraindicated in patients with active liver disease.

Antiasthmatic Agents

Zileuton is an asthma drug that differs chemically and pharmacologically from other antiasthmatic agents. It blocks leukotriene synthesis by inhibiting 5-lipoxygenase, an enzyme of the eicosanoid synthesis pathway. Current data indicates that asthma is a chronic inflammatory disorder of the airways involving the production and activity of several endogenous inflammatory mediators, including leukotrienes. Sulfido-peptide leukotrienes (LTC4, LTD4, LTE4, also known as the slow-releasing substances of anaphylaxis) and LTB4, a chemoattractant for neutrophils and eosinophils, are derived from the initial unstable product of arachidonic acid metabolism, leukotriene A4 (LTA4), and can be measured in a number of biological fluids including bronchoalveolar lavage fluid (BALF) from asthmatic patients. In humans, pretreatment with zileuton attenuated bronchoconstriction caused by cold air challenge in patients with asthma.

Compounds that bind to and inhibit that enzymatic activity of LIPOXYGENASES. Included under this category are inhibitors that are specific for lipoxygenase subtypes and act to reduce the production of LEUKOTRIENES. (See all compounds classified as Lipoxygenase Inhibitors.)|Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)|A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level. (See all compounds classified as Leukotriene Antagonists.)

Rapidly and almost completely absorbed. The absolute bioavailability is unknown.|Elimination of zileuton is predominantly via metabolism with a mean terminal half-life of 2.5 hours. The urinary excretion of the inactive N-dehydroxylated metabolite and unchanged zileuton each accounted for less than 0.5% of the dose.|1.2 L/kg|Apparent oral cl=7 mL/min/kg

Hepatic. Zileuton and its N-dehydroxylated metabolite are oxidatively metabolized by the cytochrome P450 isoenzymes 1A2, 2C9 and 3A4.|Zileuton has known human metabolites that include Zileuton O-glucuronide.

2.5 hours

Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Zileuton relieves such symptoms through its selective inhibition of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic acid. Specifically, it inhibits leukotriene LTB4, LTC4, LTD4, and LTE4 formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems. Due to the role of leukotrienes in the pathogenesis of asthma, modulation of leukotriene formation by interruption of 5-lipoxygenase activity may reduce airway symptoms, decrease bronchial smooth muscle tone, and improve asthma control.

A 64077

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients