In-vivo effects of ivermectin on Rhipicephalus appendiculatus: the influence of tick feeding patterns and drug pharmacokinetics.

Sublethal effects seen amongst Rhipicephalus appendiculatus feeding on ivermectin-treated rabbits were diverse and dependent both on drug dose, pharmacokinetics and tick feeding patterns: changes in drug formulation, the time of infestation relative to treatment, and the tick instar used, profoundly influenced acaricidal activity. Death was a sequel to paralysis only if tick feeding was interrupted for sufficient time to produce irreversible dehydration. Concurrent pharmacokinetic investigations revealed that, for the larvae of R. appendiculatus, the mean critical lethal dose of ivermectin imbibed over a 5-day engorgement period was 3500 micrograms/kg. This quantity of ivermectin was achieved in the blood-meals of larvae feeding on rabbits treated subcutaneously with a single dose of Ivomec injection (MSD)* greater than or equal to 800 micrograms/kg, provided infestation took place within 24 h of treatment. At lower drug doses, or if larval infestations were delayed for greater than 24 h post-treatment, the quantity of circulating ivermectin (and thus imbibed by the tick larvae) fell below 3500 micrograms/kg and an increasing percentage of larvae successfully engorged and detached. More than 90% of such larvae moulted to the nymphal stage. Nymphae and larvae exhibited similar susceptibility to ivermectin on treated rabbits which could be explained by similar feeding patterns. However, adult female and male ticks were markedly less susceptible and interpretation of ivermectin-induced effects was more complex.