B) showed resistance. Seasonal flu From 2009 to 2014, oseltamivir resistance was very low in seasonal flu. In the 2010–11 flu season, 99.1% of H1N1, 99.8% of H3N, and 100% of Influenza B remained oseltamivir susceptible in the US. In January 2012, the US and European CDCs reported all seasonal flu samples tested since October 2011 to be oseltamivir susceptible. In the 2013–14 season only 1% of 2009 H1N1 viruses showed oseltamivir resistance. No other influenza viruses were resistant to oseltamivir. H3N2 Three studies have found resistance in 0%, 3.3%, and 18% of subjects. In the study with the 18% resistance rate, the subjects were children, many of whom had not been previously exposed to influenza and therefore had a weakened immune response; the results suggest that higher and earlier dosing may be necessary in such populations. Influenza B In 2007, Japanese investigators detected neuraminidase-resistant influenza B virus strains in individuals not treated with these drugs. The prevalence was 1.7%. According to the CDC, , transmission of oseltamivir-resistant influenza B virus strains—from persons treated with the drug—is rare. H5N1 Avian influenza "Bird flu" , H274Y and N294S mutations that confer resistance to oseltamivir have been identified in a few H5N1 isolates from infected patients treated with oseltamivir, and have emerged spontaneously in Egypt. H7N9 Avian influenza , two of 14 adults infected with A(H7N9) and treated with oseltamivir developed oseltamivir-resistant virus with the Arg292Lys mutation. Pharmacokinetics Its oral bioavailability is over 80% and is extensively metabolised to its active form upon first-pass through the liver. It has a volume of distribution of 23–26 litres. Its half-life is about 1–3 hours and its active carboxylate metabolite has a half-life of 6–10 hours. More than 90% of the oral dose is eliminated in the urine as the active metabolite. History Oseltamivir was discovered by scientists at Gilead Sciences using shikimic acid as a starting point for synthesis; shikimic acid was originally available only as an extract of Chinese star anise; but by 2006, 30% of the supply was manufactured recombinantly in E. coli. Gilead exclusively licensed their relevant patents to Roche in 1996. The drug's patent has not been protected in Thailand, the Philippines, Indonesia, and several other countries. In 1999, the FDA approved oseltamivir phosphate for the treatment of influenza in adults based on two double-blind, randomized, placebo-controlled clinical trials. In June 2002, the European Medicines Agency (EMA) approved oseltamivir phosphate