Reproductive safety of an amino-acetonitrile derivative (AAD), monepantel, in rams following repeated oral administration

Abstract

Repeated oral administration of monepantel at three times the MRD every 5 days over an entire spermatogenic cycle and during mating was not associated with any treatment-related adverse effects on the reproductive performance of rams and was systemically very well tolerated. This study demonstrated that this population of rams could tolerate accidental overdoses of up to three times the MRD of monepantel or prolonged repetitive administration at overdoses. Thus, those so treated entering a breeding programme would have normal sperm indices, mating behaviour, and health.

Effect of route of administration on the efficacy and pharmacokinetics of an experimental formulation of the amino‐acetonitrile derivative monepantel in sheep

“…Hennessy and Prichard (1979) suggested that the deaths of cattle administered high volumes of the benzimidazole drug thiabendazole could have occurred after rumen bypass directed lethal concentrations of the drug to the abomasum. Similar results were not experienced either in this study or in ovine target animal safety studies conducted with monepantel, in which recently weaned lambs received eight doses of up to five times the recommended maximum dose at three‐weekly intervals (Malikides and others 2009b), or in adult male and female sheep treated every five days at three times the recommended dose over full reproductive cycles (Malikides and others 2009a, c).…”

“…Similar results were not experienced either in this study or in ovine target animal safety studies conducted with monepantel, in which recently weaned lambs received eight doses of up to five times the recommended maximum dose at three-weekly intervals (Malikides and others 2009b), or in adult male and female sheep treated every five days at three times the recommended dose over full reproductive cycles (Malikides and others 2009a, c). …”