Breed-related plasma disposition and faecal excretion of eprinomectin after subcutaneous administration in sheep

Abstract

Eprinomectin is a member of the avermectin family, exhibiting a broad-spectrum activity as well as a minimal elimination by milk in lactating animals. It is known that pharmacokinetic parameters are fundamental to the rational use of a drug and food safety and these parameters are influenced by different factors. The study aimed to evaluate the plasma dispositions faecal excretion profiles of eprinomectin in Awassi and Cukurova Meat Sheep (CMS) following subcutaneous administration at a dose of 0.2 mg/kg body weight. Heparinized blood and faecal samples were collected at various times between 1 h and 21 days. The plasma and faecal concentrations of eprinomectin were analysed by high-performance liquid chromatography using a fluorescence detector following a liquid-liquid phase extraction procedure. It was observed that eprinomectin concentrations in plasma and faeces were significantly affected by breed. The plasma Tlast, Cmax, AUClast, AUC0-∞, AUMClast, and AUMC0-∞ parameters of eprinomectin were significantly higher (P < 0.014) in Awassi sheep (13.88 ± 1.55 d, 29.81 ± 9.03 ng/mL, 108.05 ± 12.36 ng.d/mL, 116.07 ± 9.35 ng.d/mL, 347.77 ± 40.33 ng.d2/mL, and 486.56 ± 166.25 ng.d2/mL, respectively) compared to CMS (10.00 ± 0.00 d, 19.76 ± 4.51 ng/mL, 64.81 ± 10.54 ng.d/mL, 69.41 ± 10.98 ng.d/mL, 192.00 ± 36.12 ng.d2/mL, and 254.19 ± 52.55 ng.d2/mL, respectively). Similarly, the faecal Cmax, AUClast, and AUC0-∞ parameters of eprinomectin were detected significantly greater in Awassi sheep (3373.27 ± 1499.88 ng/g, 12,428.38 ± 2969.69 ng.d/g, and 12,668.39 ± 3047.32 ng.d/g, respectively) than CMS (2192.57 ± 323.99 ng/g, 9622.78 ± 1356.47 ng.d/g, and 9737.12 ± 1390.92 ng.d/g, respectively). The pharmacokinetic differences of eprinomectin observed between sheep breeds could be attributable to physiological characteristics such as the body fat composition of each breed. In addition, the faecal eprinomectin concentrations were about 110 times higher than those in the plasma of both sheep breeds. In line with the data obtained, eprinomectin found in high concentration in faeces may cause ecotoxicological risk for dung fauna and aquatic organisms having high sensitivity to this compound.