Steady-state levels of hydroxyflutamide, the active form of flutamide, are achieved after 2 to 4 days administration. Levels of hydroxyflutamide are approximately 50-fold higher than those of flutamide at steady-state.The plasma protein binding of flutamide and hydroxyflutamide are high; 94 to 96% and 92 to 94%, respectively. Flutamide and its metabolite hydroxyflutamide are known to be transported by the multidrug resistance-associated protein 1 (MRP1; ABCC1).Flutamide is metabolized by CYP1A2 (via α-hydroxylation) in the liver during first-pass metabolism to its main metabolite hydroxyflutamide (which accounts for 23% of an oral dose of flutamide one hour post-ingestion), and to at least five other, minor metabolites. Flutamide has at least 10 inactive metabolites total, including 4-nitro-3-fluoro-methylaniline.Flutamide is excreted in various forms in the urine, the primary form being 2-amino-5-nitro-4-(trifluoromethyl)phenol.Flutamide and hydroxyflutamide have elimination half-lives of 4.7 hours and 6 hours in adults, respectively. However, the half-life of hydroxyflutamide is extended to 8 hours after a single dose and to 9.6 hours at steady state) in elderly individuals. The elimination half-lives of flutamide and hydroxyflutamide are regarded as too short to allow for once-daily dosing, and for this reason, flutamide is instead administered three times daily at 8-hour intervals. In contrast, the newer NSAAs nilutamide, bicalutamide, and enzalutamide all have much longer half-lives, and this allows for once-daily administration in their cases. Chemistry
Unlike the hormones with which it competes, flutamide is not a steroid; rather, it is a substituted anilide.
Lassa fever, also known as Lassa hemorrhagic fever (LHF), is a type of viral hemorrhagic fever caused by the Lassa virus. Many of those infected by the virus do not develop symptoms. When symptoms occur they typically include fever, weakness, headaches, vomiting, and muscle pains. Less commonly there may be bleeding from the mouth or gastrointestinal tract. The risk of death once infected is about one percent and frequently occurs within two weeks of the onset of symptoms. Of those who survive, about a quarter have hearing loss, which improves within three months in about half of these cases.The disease is usually initially spread to people via contact with the urine or feces of an infected multimammate mouse. Spread can then occur via direct contact between people. Diagnosis based on symptoms is difficult. Confirmation is by laboratory testing to detect the viruss RNA, antibodies for the virus, or the virus itself in cell culture. Other conditions that may present similarly include Ebola, malaria, typhoid fever, and yellow fever. The Lassa virus is a member of the Arenaviridae family of viruses.There is no vaccine. Prevention requires isolating those who are infected and decreasing contact with the mice. Other efforts to control the spread of disease include having a cat to hunt vermin, and storing food in sealed containers. Treatment is directed at addressing dehydration and improving symptoms. The antiviral medication ribavirin has been recommended, but evidence to support its use is weak.Descriptions of the disease date from the 1950s.