A Comprehensive Pharmacological and Clinical Monograph on Zileuton

1.0 Introduction and Chemical Profile

1.1 Overview and Therapeutic Class

Zileuton is an orally active inhibitor of the 5-lipoxygenase (5-LOX) enzyme, positioning it within a distinct class of anti-inflammatory agents used for the prophylaxis and chronic treatment of asthma.[1] Its chemical structure and pharmacological mechanism differ significantly from other antiasthmatic drugs, particularly the more widely used leukotriene receptor antagonists (LTRAs) such as montelukast and zafirlukast.[1] While LTRAs block the action of leukotrienes at their receptor sites, zileuton acts upstream to prevent their synthesis altogether. This distinction is fundamental to understanding its efficacy and side effect profile.

The clinical history of zileuton is complex; it is an approved medication, but its immediate-release (IR) formulation was withdrawn from the United States market, while an extended-release (ER) version remains available.[1] This history reflects a balance between its therapeutic utility and challenges related to dosing convenience and safety monitoring.

1.2 Physicochemical Properties and Formulation

Zileuton is a synthetic organic compound with a well-defined chemical profile. Its systematic International Union of Pure and Applied Chemistry (IUPAC) name is 1-[1-(1-benzothiophen-2-yl)ethyl]-1-hydroxyurea.[9] It is also known by several synonyms, including (±)-1-(1-Benzo[b]thien-2-ylethyl)-1-hydroxyurea and the development code A-64077.[1]

The drug is a racemic mixture, composed of a 50:50 ratio of its R(+) and S(-) enantiomers. Both enantiomers have been shown to be pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems, meaning the entire mixture contributes to the therapeutic effect.[1]