Anthelmintic Efficacy and Pharmacokinetics of Ivermectin Paste after Oral Administration in Mules Infected by Cyathostomins

SIMPLE SUMMARY: Mules and donkeys are often treated as horses from a therapeutic point of view. This approach could be dangerous due to species differences in drug pharmacokinetics which could reflect on the drug effectiveness. Ivermectin is a commonly used anthelmintic compound due to the broad spectrum of activity. The improper use of ivermectin (i.e., dosage, route of administration) could cause a lack of parasite control and contribute to development of drug resistance. Studies on the pharmacokinetics and efficacy of antiparasitic molecules in mules are limited, although these drugs are crucial for the welfare of these equines. The aim of the present study was to evaluate the efficacy and pharmacokinetics of ivermectin administered to mules at the same dosage (200 µg/kg body weight) and route licensed for horses. Results show that administering ivermectin orally, at the same dosage of horses, has a pharmacokinetic intermediate behavior between horses and donkeys. This study demonstrates that ivermectin oral paste at horse dosage is effective and safe for the treatment of cyathostomins in mules. ABSTRACT: Ivermectin (IVM) is an anthelmintic compound commonly used off-label in mules due to its broad-spectrum of activity. Despite the general use of IVM in mules with the same dose and route of administration licensed for horses, significant pharmacokinetic differences might exist between horses and mules, as already observed for donkeys. The aim of the present study was to evaluate the pharmacokinetic profile and anthelmintic efficacy of an oral paste of IVM in mules naturally infected with cyathostomins. Fifteen adult mules with fecal egg counts (FEC) ≥ 200 eggs per gram (EPG), with exclusive presence of cyathostomins, were included in the study. All mules were orally treated with IVM according to the manufacturer's recommended horse dosage (200 µg/kg body weight). FECs were performed before (day-10 and day-3) and after treatment at days 14 and 28 by using a modified McMaster method. The FEC reduction (FECR%) was also calculated. Blood samples were collected from five animals at various times between 0.5 h up to 30 days post treatment to determine pharmacokinetic parameters. The maximum IVM serum concentration (Cmax) was 42.31 ± 10.20 ng/mL and was achieved at 16.80 ± 9.96 h post-treatment (Tmax), area under the curve (AUC) was 135.56 ± 43.71 ng × day/mL. FECR% remained high (>95%) until the 28th day.