The Safety and Efficacy of Zileuton Controlled-Release Tablets as Adjunctive Therapy to Usual Care in the Treatment of Moderate Persistent Asthma: A 6-Month Randomized Controlled Study

Wenzel, Sally E.; Busse, William W.; Calhoun, William J.; Panettieri, Reynold A.; Peters-Golden, Mark; Dubé, Louise M.; Walton–Bowen, Karen; Russell, Heidy K.; Harris, James A.

doi:10.1080/02770900701344199

Cited by 27 publications

(16 citation statements)

References 11 publications

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“…Unfortunately, zileuton – the only marketed inhibitor of LT biosynthesis – has not been widely used because of 1) the initial need to take it 4 times daily (a controlled-release tablet can now be used twice daily) and 2) the requirement for liver function test monitoring due to possible hepatocellular injury [112]. In addition, although no head-to-head comparisons between zileuton and a LTRA have ever been conducted, there is no compelling evidence that zileuton is typically superior to LTRAs in asthma treatment [113, 114]. Incomplete efficacy may be due to the incomplete inhibition (26 to 86 % inhibition) of LT synthesis by zileuton [115].…”

Section: Anti-lt Drugsmentioning

confidence: 99%

Leukotrienes and airway inflammation

Okunishi

Peters‐Golden

2011

Biochimica et Biophysica Acta (BBA) - General Subjects

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Asthma is a common chronic inflammatory disease of the airways characterized by airway obstruction and hyperresponsiveness. Leukotrienes (LTs) are lipid mediators that contribute to many aspects of asthma pathogenesis. As the LT pathway is relatively steroid-resistant, its blockade by alternative strategies is a desirable component of asthma management. Cysteinyl LT receptor 1 antagonists have been utilized worldwide for more than 10 years, and while their efficacy in asthma is well accepted, their limitations are also evident. In this review, we summarize the biological effects of LTs in asthma, review recent advances in LT receptors, and consider possible new therapeutic targets in the LT pathway that offer the potential to achieve better control of asthma in the future.

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Section: Anti-lt Drugsmentioning

confidence: 99%

Leukotrienes and airway inflammation

Okunishi

Peters‐Golden

2011

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…Hepatitis has been reported with chronic zafirlukast which resulted in hepatic failure requiring liver transplant and death. The chronic use of zileuton use has also resulted in elevated liver enzymes in about 5 % of asthma patients [79,80].…”

Section: Leukotriene Modulatorsmentioning

confidence: 99%

The Acute Management of Asthma

Albertson

Sutter

Chan

2014

Clinic Rev Allerg Immunol

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Patients presenting to the emergency department (ED) or clinic with acute exacerbation of asthma (AEA) can be very challenging varying in both severity and response to therapy. High-dose, frequent or continuous nebulized short-acting beta2 agonist (SABA) therapy that can be combined with a short-acting muscarinic antagonist (SAMA) is the backbone of treatment. When patients do not rapidly clinically respond to SABA/SAMA inhalation, the early use of oral or parenteral corticosteroids should be considered and has been shown to impact the immediate need for ICU admission or even the need for hospital admission. Adjunctive therapies such as the use of intravenous magnesium and helium/oxygen combination gas for inhalation and for driving a nebulizer to deliver a SABA and or SAMA should be considered and are best used early in the treatment plan if they are likely to impact the patients' clinical course. The use of other agents such as theophylline, leukotriene modifiers, inhaled corticosteroids, long-acting beta2 agonist, and long-acting muscarinic antagonist currently does not play a major role in the immediate treatment of AEA in the clinic or the ED but is an important therapeutic option for physicians to be aware of and to consider initiating at the time of discharge from clinic, hospital, or ED to reduce later clinical worsening and readmission to the ED and hospital. A comprehensive summary is provided of the currently available respiratory pharmaceuticals approved for asthma and other airway syndromes. Clinicians must be prepared to use the entire spectrum of medications available for the treatment of acute asthma exacerbations and the agents that should be initiated to prevent worsening or additional exacerbations. They need to be familiar with the major potential drug toxicities associated with their use.

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“…This is the same level of sequence identity observed between 5-LOX and its closest intra-species orthologue 15-LOX-2. Human 5-LOX is the only clinically validated drug target of the LOX family, but the enzyme’s short half-life has made biochemical characterization difficult (Carter et al, 1991; Percival, Denis, Riendeau, & Gresser, 1992; Wenzel et al, 2007). The extraordinary stability of the coral enzyme makes it a highly tractable system for structural studies, as protein instability is a frequent roadblock to structural studies (Deller, Kong, & Rupp, 2016), and 8 R -LOX structures have revealed key mechanistic details of the LOX oxygenation reaction.…”

Section: Introductionmentioning

confidence: 99%

Expression of an 8 R -Lipoxygenase From the Coral Plexaura homomalla

Gilbert

Neau

Newcomer

2018

Marine Enzymes and Specialized Metabolism - Part B

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Methods are presented for the use of the coral 8R-lipoxygenase from the Caribbean sea whip coral Plexaura homomalla as a model enzyme for structural studies of animal lipoxygenases. The 8R-lipoxygenase is remarkably stable and can be stored at 4°C for 3 months with virtually no loss of activity. In addition, an engineered "pseudo wild-type" enzyme is soluble in the absence of detergents, which helps facilitate the preparation of enzyme:substrate complexes.

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The Safety and Efficacy of Zileuton Controlled-Release Tablets as Adjunctive Therapy to Usual Care in the Treatment of Moderate Persistent Asthma: A 6-Month Randomized Controlled Study

Cited by 27 publications

References 11 publications

Leukotrienes and airway inflammation

Leukotrienes and airway inflammation

The Acute Management of Asthma

Expression of an 8 R -Lipoxygenase From the Coral Plexaura homomalla

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