Inhalation of an Ethanol-Based Zileuton Formulation Provides a Reduction of Pulmonary Adenomas in the A/J Mouse Model

Potential efficacy of zileuton, a 5-LOX inhibitor, was evaluated for the reduction of pulmonary adenomas in the A/J murine model when administered via nose-only inhalation. Development of pulmonary adenomas was induced with benzo(a)pyrene. Animals were treated with a zileuton solution (5 mg/mL in 85:15 ethanol/water) either twice weekly or five times a week via nose-only inhalation; The placebo solution (85:15 EtOH/H₂O, no active) was also evaluated. Dose delivered was calculated to be 1.2 mg/kg per exposure for each zileuton group. After 20 weeks of treatment, surface tumors were enumerated and histologically assessed. A significant reduction in tumor count was noted for both the twice weekly administration (40%) and the five times a week administration (59%). The data also showed a significant reduction for the group, which received the placebo (approximately 58%). The treatment groups were also found to have an impact on the histological stages of adenoma development.