Ivermectin CRS

개요Ivermectin is an antiparasitic agent effective in the treatment of onchocerciasis, or "river blindness". Since ivermectin acts to prevent the adult worm from producing microfilariae, it needs to be administered only once or twice a year.

역사The discovery of ivermectin was the result of a landmark collaboration in the 1970s between Merck & Co. and the Kitasato Institute in Japan. Microbiologist Satoshi Ōmura isolated a new Streptomyces species—Streptomyces avermitilis—from Japanese soil and sent its cultures to Merck. Merck scientist William C. Campbell then discovered ivermectins, a natural product with potent anthelmintic activity. To reduce its toxicity to mammals and optimize its efficacy, Merck chemists performed semi-synthetic modifications on ivermectin, hydrogenating it to obtain the derivative ivermectin. This optimization significantly improved the drug's safety, leading to its market launch as a highly effective veterinary drug in 1981. Its historic contribution lies in its application in human medicine: after demonstrating its remarkable efficacy against river blindness, Merck decided in 1987 to donate ivermectin (Mectizan®) indefinitely for the control and elimination of river blindness and lymphatic filariasis worldwide. This achievement ultimately earned Satoshi Ōmura and Campbell the 2015 Nobel Prize in Physiology or Medicine.

The synthesis of ivermectin involves the hydrogenation of the naturally occurring avermectin B1 (abamectin) at the double bond linking C-22 and C-23. This results in a mixture of two homologues, 22, 23-dihydroavermectin B1a (H2B1a) and 22, 23-dihydroavermectin B1b (H2 B1b). The a- and b- nomenclature refers to the presence on C-25, of either a secondary butyl side chain or an isopropyl group, respectively. The biological activities of H2B1a and H2B1b are similar. Large-scale separation of the two homologues is not practical, and, hence, ivermectin is marketed as a mixture of H2 B1a (>80%) and H2 B1b (