Ivermectin metabolism

Zeng Z, Andrew NW, Arison BH, Luf-fer-Atlas D, Wang RW. Identification of cytochrome P4503A4 as the major enzyme responsible for the metabolism of ivermectin by human liver chromosomes. Xenobiotica 1998 28 313-321. 

Following the oral administration of ivermectin, peak plasma concentration is achieved in four hours. Ivermectin is absorbed well on an empty stomach. The bioavailability is 50 to 60%. It is mainly metabolized in the liver and the tissue concentration is maximum in liver and fat. Ivermectin and its metabolites are excreted mainly in faeces. 

Metabolism studies showed that the major metabolites of the components of ivermectin in cattle, sheep, and rats were 24-hydroxymethyl compounds, whereas major metabolites in swine were 3-0-desmethyl compounds. Identification of the 24-hydroxymethyl metabolites has not been yet achieved in swine, whereas identification of Hie 3-O-desmetlryl metabolites has not been made possible in cattle or sheep (54, 55). Recent metabolism studies (56) in cattle, swine, and rats have indicated, however, diat the metabolism of avermectins was qualitatively similar for all three species. There were quantitative differences both between species and between compounds for a given species, but all three species produced... 

The interaction between acenocoumarol and ivermectin with methidathion is not understood. When used on its own, ivermectin used for onchocerciasis normally has no effect on prothrombin times, but two unexplained cases of prolonged prothrombin times associated with the development of haematomas have been reported. Methidathion is an organophosphate. Lindane and other chlorinated hydrocarbon insecticides are known liver enzyme inducers, which increase the metabolism and clearance of the warfarin, thereby reducing or even abolishing its effects. 

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