In a separate chemical step, the mixture is hydrogenated to give ivermectin, which is an approximately 80:20 mixture of the two 22,23-dihydroavermectin compounds.Ivermectin is a macrocyclical lactone. History
The avermectin family of compounds was discovered by Satoshi Ōmura of Kitasato University and William Campbell of Merck. In 1970, Ōmura isolated a strain of Streptomyces avermitilis from woodland soil near a golf course along the south east coast of Honshu, Japan. Ōmura sent the bacteria to William Campbell, who showed that the bacterial culture could cure mice infected with the roundworm Heligmosomoides polygyrus. Campbell isolated the active compounds from the bacterial culture, naming them "avermectins" and the bacterium Streptomyces avermitilis for the compounds ability to clear mice of worms (in Latin: a without, vermis worms). Of the various avermectins, Campbells group found the compound "avermectin B1" to be the most potent when taken orally. They synthesized modified forms of avermectin B1 to improve its pharmaceutical properties, eventually choosing a mixture of at least 80% 22,23-dihydroavermectin B1a and up to 20% 22,23-dihydroavermectin B1b, a combination they called "ivermectin".The discovery of ivermectin has been described as a combination of "chance and choice." Merck was looking for a broad-spectrum anthelmintic, which ivermectin is indeed; however, Campbell noted that they "...also found a broad-spectrum agent for the control of ectoparasitic insects and mites. "Merck began marketing ivermectin as a veterinary antiparasitic in 1981. By 1986, ivermectin was registered for use in 46 countries and was administered massively to cattle, sheep and other animals.
Worm infections
For river blindness (onchocerciasis) and lymphatic filariasis, ivermectin is typically given as part of mass drug administration campaigns that distribute the drug to all members of a community affected by the disease. For river blindness, a single oral dose of ivermectin (150 micrograms per kilogram of body weight) clears the body of larval Onchocerca volvulus worms for several months, preventing transmission and disease progression. Adult worms survive in the skin and eventually recover to produce larval worms again; to keep the worms at bay, ivermectin is given at least once per year for the 10–15-year lifespan of the adult worms. For lymphatic filariasis, oral ivermectin (200 micrograms per kilogram body weight) is part of a combination treatment given annually: ivermectin, diethylcarbamazine citrate and albendazole in places without onchocerciasis; and ivermectin and albendazole in places with onchocerciasis.The World Health Organization (WHO) considers ivermectin the drug of choice for strongyloidiasis. Most cases are treated with two daily doses of oral ivermectin (200 μg per kg body weight), while severe infections are treated with five to seven days of ivermectin. Ivermectin is also the primary treatment for Mansonella ozzardi and cutaneous larva migrans. The U.S. Centers for Disease Control and Prevention (CDC) recommends ivermectin, albendazole, or mebendazole as treatments for ascariasis. Ivermectin is sometimes added to albendazole or mebendazole for whipworm treatment, and is considered a second-line treatment for gnathostomiasis. Mites and insects
Ivermectin is also used to treat infection with parasitic arthropods.