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.
Galactorrhea (also spelled galactorrhoea) (galacto- + -rrhea) or lactorrhea (lacto- + -rrhea) is the spontaneous flow of milk from the breast, unassociated with childbirth or nursing. Galactorrhea is reported to occur in 5–32% of women. Much of the difference in reported incidence can be attributed to different definitions of galactorrhea. Although frequently benign, it may be caused by serious underlying conditions and should be properly investigated. Galactorrhea also occurs in males, newborn infants and adolescents of both sexes. Causes
Galactorrhea can take place as a result of dysregulation of certain hormones. Hormonal causes most frequently associated with galactorrhea are hyperprolactinemia and thyroid conditions with elevated levels of thyroid-stimulating hormone (TSH) or thyrotropin-releasing hormone (TRH). No obvious cause is found in about 50% of cases.Lactation requires the presence of prolactin, and the evaluation of galactorrhea includes eliciting a history for various medications or foods (methyldopa, opioids,  antipsychotics, serotonin reuptake inhibitors) and for behavioral causes (stress, breast, and chest wall stimulation), as well as evaluation for gestation, pituitary adenomas (with overproduction of prolactin or compression of the pituitary stalk), and hypothyroidism. Adenomas of the anterior pituitary are most often prolactinomas. Overproduction of prolactin leads to cessation of menstrual periods and infertility, which may be a diagnostic clue. Galactorrhea may also be caused by hormonal imbalances owing to birth control pills. Galactorrhea is also a side effect associated with the use of the second-generation H2 receptor antagonist cimetidine (Tagamet).