Pharmacokinetics, Absolute Bioavailability, and Nonlinear Topical Absorption of a Fluralaner-Moxidectin Spot-On...

Long-acting spot-on formulations are widely used for parasite control in cats, yet the pharmacokinetics of combined fluralaner and moxidectin remain incompletely defined beyond the recommended dose. This study evaluated the pharmacokinetics, absolute bioavailability, and dose proportionality of a novel fixed-combination spot-on formulation in healthy cats after topical administration of fluralaner/moxidectin at 40/2, 80/4, and 120/6 mg/kg BW, and compared intravenous administration of each compound alone or in combination. Forty-eight healthy cats were allocated to six groups of eight cats each. Non-compartmental analysis and a power model were used to characterize systemic exposure and dose proportionality. After intravenous co-administration, fluralaner exposure increased whereas moxidectin exposure decreased compared with single-agent administration, indicating a potential pharmacokinetic interaction. Topical administration produced slow absorption and sustained systemic persistence, with T_max values occurring approximately 10-18 days after dosing and quantifiable concentrations maintained throughout the 160 days sampling period. Systemic exposure increased non-proportionally across the tested dose range, and absolute bioavailability was limited and dose-dependent, ranging from 9.7% to 26.9% for fluralaner and from 10.22% to 21.28% for moxidectin. No adverse reactions were observed. These findings demonstrate nonlinear topical absorption, and prolonged systemic persistence, supporting further dose optimization and formulation development of this long-acting feline antiparasitic delivery system.