Ecotoxicity of antiparasitics: optimization of the use of pharmaceutical forms of ivermectin and its analogues

Ivermectin, together with its analogues is, worldwide, currently the most extensively used drug for treating gastrointestinal nematodes in farm animals. It is, likewise, widely used in human medicine. Through its effectiveness at very low doses, persistence, broad spectrum of action (it is also an acaricide and insecticide) and low host toxicity, it has achieved the status of the most revolutionary antiparasitic agent to be introduced in the 1980s.
For anthelmintic treatment with ivermectin, three formulations are available: a solution for subcutaneous injection; the "Pour-On", a liquid applied to the back of the animal and absorbed through the skin; and the bolus, the equivalent of a large tablet designed to dissolve very slowly in the stomach liquor of ruminants (rumen).
The research studies of INRAE and its partners focused on the efficacy and possible drawbacks of the three ivermectin formulations. The data obtained have led to significant regulatory improvements in France and abroad.
INRAE's work on ivermectin provided the stimulus for incorporating ecotoxicology data  in submissions for Marketing Authorizations. This resulted in withdrawal of the SR (slow release) bolus Marketing Authorization. A highly positive outcome has been avoidance of excretion, in massive amounts, of ivermectin by the faecal route. It had positive benefits on ecosystems, in particular those most fragile, on mountainous summer-dry pastures.

Henceforth, the compulsory incorporation of ecotoxicity in the marketing authorization dossiers for veterinary medicinal products comprises a major long term advance.
Studies carried out under field conditions, taking account of the social behaviour of animals, have been shown to be relevant to therapeutic practice. The findings are now accepted either as an alternative to or additional to those long accepted under Good Laboratory Practice guidelines.
An example is regulatory acceptance of the need to take account of the common practice of inter-animal licking, which results in oral absorption of drugs by other in-contact animals in the herd. The result has been regulatory acceptance of the revision of Data Sheets of ivermectin when it is applied to the back. 

Through this pioneering research, animal medicine has directly contributed to human health. This is an almost unique example of how the development a veterinary drug, ivermectin, fueled studies of its actions in humans, leading to its subsequent use in humans.

The body of knowledge on the properties of ivermectin in animals, obtained through the INRAE studies, was influential, in particular concerning the long persistence of ivermectin, a property which allows, with a single oral dose or when administered twice a year, to control endemic tropical parasitosis, such as onchocerciasis in at-risk inhabitants of African villages.