Systemic activity of the avermectins against the cat flea (Siphonaptera : Pulicidae)

Ivermectin has potent systemic activity against numerous species of nematod es and arthropods, but there are some important species in these two groups , such as the cat flea, Ctenocephalides felis (Bouche), that appear to be r efractory to it. In an effort to determine if tire lack of systemic activit y against C.felis is specific to ivermectin. or if it is a class-wide pheno menon, 20 avermectin derivatives were tested in artificial membrane flea fe eding system at concentrations of 20, 10, and 1 mug/ml. Results showed that ivermectin had LC90 and LC50 values against fleas of 19.1 and 9.9 mug/ml, respectively. Only four of the other 19 compounds evaluated possessed both LC90 and LC,, values more potent than ivermectin and el en then the advanta ge was modest. Among those four compounds was a two-fold increase in potenc y relative to ivermectin when the LC90 values were considered (range, 9.2-1 0.3 mug/ml) and a two- to eight-fold increase when the LC50 values were exa mined (range, 1.23-5.26 mug/ml). Neither the possession nor the number of o leandrosyl sugars on the macrocyclic backbone were relevant for additional flea activity because among these four compounds were two disaccharides, a monosaccharide and an aglycone. Also. bond disposition between C-22 and 23 did not contribute to increase in activity because these molecules comprise members with either single or double bonds. One of these avermectin analog s was scaled-up and tested subcutaneously in a dog at > 100 times the comme rcial ivermectin dosage and zero efficacy) was observed against the flea. W e conclude that even the best in vitro avermectin does not have the in vivo potential to become a commercial oral or subcutaneous nea treatment for co mpanion animals.