Ivermectin, ‘Wonder drug’ from Japan: the human use perspective
For those interested, this is an interesting read
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3043740/Abstract
Discovered in the late-1970s, the pioneering drug ivermectin, a dihydro derivative of avermectin—originating solely from a single microorganism isolated at the Kitasato Intitute, Tokyo, Japan from Japanese soil—has had an immeasurably beneficial impact in improving the lives and welfare of billions of people throughout the world. Originally introduced as a veterinary drug, it kills a wide range of internal and external parasites in commercial livestock and companion animals. It was quickly discovered to be ideal in combating two of the world’s most devastating and disfiguring diseases which have plagued the world’s poor throughout the tropics for centuries. It is now being used free-of-charge as the sole tool in campaigns to eliminate both diseases globally. It has also been used to successfully overcome several other human diseases and new uses for it are continually being found. This paper looks in depth at the events surrounding ivermectin’s passage from being a huge success in Animal Health into its widespread use in humans, a development which has led many to describe it as a “wonder” drug.
Introduction
There are few drugs that can seriously lay claim to the title of ‘Wonder drug’, penicillin and aspirin being two that have perhaps had greatest beneficial impact on the health and wellbeing of Mankind. But ivermectin can also be considered alongside those worthy contenders, based on its versatility, safety and the beneficial impact that it has had, and continues to have, worldwide—especially on hundreds of millions of the world’s poorest people. Several extensive reports, including reviews authored by us, have been published detailing the events behind the discovery, development and commercialization of the avermectins and ivermectin (22,23-dihydroavermectin B), as well as the donation of ivermectin and its use in combating Onchocerciasis and lymphatic filariasis.1–6) However, none have concentrated in detail on the interacting sequence of events involved in the passage of the drug into human use.
When it first appeared in the late-1970s, ivermectin, a derivative of avermectin (Fig. (Fig.1)1) was a truly revolutionary drug, unprecedented in many ways. It was the world’s first endectocide, forerunner of a completely new class of antiparasitic agents, potently active against a wide range of internal and external nematodes and arthropods. In the early-1970s, a novel international Public Sector–Private Sector partnership was initiated by one of us (Ōmura, then head of the Antibiotics Research Group at Tokyo’s Kitasato Institute), forming a collaboration with the US-based Merck, Sharp and Dohme (MSD) pharmaceutical company. Under the terms of the research agreement, researchers at the Kitasato Institute isolated organisms from soil samples and carried out preliminary invitro evaluation of their bioactivity. Promising bioactive samples were then sent to the MSD laboratories for further invivo testing where a potent and promising novel bioactivity was found, subsequently identified as being caused by a new compound, which was named ‘avermectin’.7) Despite decades of searching around the world, the Japanese microorganism remains the only source of avermectin ever found.1) Originating from a single Japanese soil sample and the outcome of the innovative, international collaborative research partnership to find new antiparasitics, the extremely safe and more effective avermectin derivative, ivermectin, was initially introduced as a commercial product for Animal Health in 1981. It is effective against a wide range of parasites, including gastrointestinal roundworms, lungworms, mites, lice and hornflies.7–12) Ivermectin is also highly effective against ticks, for example, the ixodid tick Rhipicephalus (Boophilus) microplus, one of the most important cattle parasites in the tropics and subtropics, which causes enormous economic damage. Indicative of the impact, in Brazil, where some 80% of the bovine herd is infested, losses total about $2 billion annually.13) Today, ivermectin is being used to treat billions of livestock and pets around the world, helping to boost production of food and leather products, as well as keep billions of companion animals, particularly dogs and horses, healthy. The ‘Blockbuster’ drug in the Animal Health sector, meaning that it achieved annual sales in excess of over US$1 billion, maintained that status for over 20 years. It is so useful and adaptable that it is also being used off-label, sometimes, illegally, for example to treat fish lice in the aquaculture industry, where it can have a negative impact on non-target organisms. It also has extensive uses in agriculture.2)
