Leukotriene Modifiers

Zafirlukast - Accolate® Tablets

• Indications: Prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older

• MOA: selective and competitive leukotriene receptor cysLT1 antagonist of leukotriene L T D4 and L TE4 which are components of SRS-A preventing bronchoconstriction

• Metabolism: Extensively metabolized by CYP2C9 and CYP3A4 yet Inhibits CYP3A4 and CYP2C9

• Do not use to treat acute attacks, nursing women should NOT use this drug one hour before or two hours after a meal

Zafirlukast - Accolate® Tablets structure

Montelukast Sodium - Singulair®

Indications: Prophylaxis and chronic treatment of asthma in adults and children one year of age and older; 4 mg oral granules for children 0.5 - 5 years old for perennial allergic rhinitis

MOA: selective and competitive cysLT1 receptor antagonist of leukotriene LTC3, LTD4 and L TE4 which are components of SRS-A preventing bronchoconstriction

Metabolism: Metabolized by CYP2C9 and CYP3A4

Tablets and Chewable tablets, oral granules - once daily in the evening and with or without food

Montelukast Sodium - Singulair® structure

Zileuton - ZYFLO CR® Extended-release tablets

• Indications: Prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older

• SAR: 1) the N-hydroxy is essential for inhibitory activity; 2) the benzothienyl contributing to lipophilicity

• MOA: orally active inhibitor of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic to LTB4, LTC4, LTD4 and LTE4 - Both the R(+) and S(-) enantiomers are pharmacologically active

• Metabolism: Zileuton and its N-dehydroxylated metabolite can be oxidatively metabolized by CYP1A2, CYP2C9 and CYP3A4 followed by glucuronidation -contraindicated in patients with active liver disease or persistent ALT elevations

• DI’s: Drug interactions with theophylline and warfarin

Zileuton - ZYFLO CR® Extended-release tablets structure