Plasma Pharmacokinetic Profile of Fipronil 1% Pour-On in Cattle: Photodegradation and the Sustained Systemic Persistence of Fipronil Sulfone

Abstract

This study characterized the long-term pharmacokinetic profile of a 1% fipronil pour-on formulation in Nellore bulls under field conditions. Seventeen animals received a single topical dose (1 mg/kg), and plasma concentrations of fipronil and its metabolites (sulfone and desulfinyl) were monitored for 175 days using LC–MS/MS. Fipronil was rapidly absorbed, reaching a maximum concentration C_max of 42.3 ± 4.1 ng/mL on day 1, but became undetectable by day 35. Conversely, fipronil sulfone was the predominant systemic analyte, reaching C_max 60.2 ± 5.6 ng/mL on day 13 and persisting for up to 140 days. The metabolite-to-parent AUC_0–t ratio (6.2) and the protracted terminal phase are consistent with flip-flop kinetics, where systemic persistence is governed by slow release from the dermal/sebaceous reservoir rather than metabolic clearance. Fipronil desulfinyl was sporadically detected at low levels, confirming that in vivo photodegradation occurs on the animal's surface. These findings consolidate fipronil sulfone as the most reliable marker residue for food safety assessments. Furthermore, the sporadic detection of fipronil desulfinyl confirms that in vivo photodegradation occurs under field conditions, warranting further investigation regarding its contribution to residue dynamics in cattle.