Plasma pharmacokinetic profile of fipronil 1% pour-on in goats

Fipronil is a phenylpyrazole insecticide widely used in agriculture and veterinary medicine, but there are currently no licensed formulations for goats, leading to extra-label use and raising food safety concerns. This study aimed to characterize the plasma pharmacokinetic profile of fipronil and its primary active metabolite, fipronil sulfone, in goats following topical administration. Eight female Alpine Brown goats received a single dose of a 1% fipronil pour-on formulation (1 mg/kg). Blood samples were collected up to 117 days post-treatment and analyzed using high-performance liquid chromatography (HPLC). No adverse clinical effects or significant changes in health biomarkers were observed. Fipronil was rapidly detected in plasma (C max = 443.7 ± 195.8 ng/mL), followed by an extensive distribution phase and terminal elimination with a half-life (t 1/2z ) of 4.2 ± 0.8 days and total systemic exposure (AUC 0-t ) 1245.3 ± 312.5 ng·day/mL. Fipronil-sulfone exhibited delayed formation, reaching a lower peak (67.3 ± 27.3 ng/mL) with a median T max of 15.0 days and an AUC 0-t of 558.4 ± 92.1 ng day/mL. This is the first study to characterize the plasma pharmacokinetic profile of fipronil pour-on in goats. The observed systemic exposure in goats was substantially higher (over 800-fold) than previously reported for cattle, suggesting major species-specific differences in dermal absorption. The prolonged persistence and delayed metabolite formation are suggestive of- flip-flop kinetic pattern, likely governed by slow redistribution from skin and adipose reservoirs. These findings provide a preliminary pharmacokinetic background for future residue depletion studies and food safety assessments in goats. • Pioneering report on fipronil and fipronil-sulfone disposition in goats. • Flip-flop kinetics and tissue sequestration drive prolonged systemic exposure. • Distinctly high dermal bioavailability in goats compared to bovine models. • Interspecies metabolic gaps demand tailored food safety assessments. • Data provide a basis for future studies on tissue distribution and residues.