of CYP1A2 and thus has three clinically important drug interactions, which include increasing theophylline, and propranolol levels. It has been shown to lower theophylline clearance significantly, doubling the AUC and prolonging half-life by nearly 25%. Because of theophylline's relation to caffeine (both being a methylxanthine, and theophylline being a metabolite of caffeine), caffeine's metabolism and clearance may also be reduced, but there are no drug interaction studies between zileuton and caffeine. The R-isomer of warfarin metabolism and clearance is mainly affected by zileuton, while the S-isomer is not (because of metabolism via different enzymes). This can lead to an increase in prothrombin time. Chemistry Zileuton is an active oral inhibitor of the enzyme 5-lipoxygenase, which forms leukotrienes, 5-hydroxyeicosatetraenoic acid, and 5-oxo-eicosatetraenoic acid from arachidonic acid. The chemical name of zileuton is (±)-1-(1-Benzo[b]thien-2-ylethyl)-l-hydroxyurea. The molecular formula of zileuton is C11H12N2O2S with a molecular weight of 236.29. The formulation from the manufacturer is a racemic mixture of R(+) and S(-) enantiomers. Pharmacokinetics Following oral administration zileuton is rapidly absorbed with a mean time to peak blood serum concentration of 1.7 hours and an average half-life elimination of 2.5 hours. Blood plasma concentrations are proportional to dose, whereas the absolute bioavailability is unknown. The apparent volume of distribution of zileuton is approximately 1.2 L/kg. Zileuton is 93% bound to plasma proteins, primarily to albumin, with minor binding to alpha-1-acid glycoprotein. Elimination of zileuton is primarily through metabolites in the urine (~95%) with the feces accounting for the next largest amount (~2%). The drug is metabolized by the cytochrome P450 enzymes: CYP1A2, 2C9, and 3A4. Adverse effects The most common adverse reactions reported by patients treated with Zyflo CR were sinusitis (6.5%), nausea (5%), and pharyngolaryngeal pain (5%) vs. placebo, 4%, 1.5%, and 4% respectively. Interactions Drug interactions Zileuton is a minor substrate of CYP1A2, 2C8/9, 3A4, and a weak inhibitor of CYP 1A2. The drug has been shown to increase the serum concentration or effects of theophylline, propranolol, and warfarin, although significant increase in prothrombin time is not obvious. It is advised that the doses of each medication be monitored and/or reduced accordingly. Other interactions The avoidance of alcohol is recommended due to increased risk of CNS depression as well as an increased risk of liver toxicity. In addition, the herbal supplement St. John's wort may decrease the serum levels of zileuton. Overdose/toxicology Symptoms Human experience of acute overdose with zileuton is limited.