Pharmacokinetics and preliminary safety of single-dose oral fluralaner at 10 and 25 mg/kg in healthy horses revealed no adverse reactions.

Overview

• This study evaluated the safety and pharmacokinetics of a single oral dose of fluralaner, an ectoparasiticide, at 10 mg/kg and 25 mg/kg in healthy horses.
• The research found that fluralaner was absorbed and persisted in the blood and skin without causing adverse effects, indicating it is safe and potentially effective for treating some horse parasites.

Study Objectives and Design

• Objective: To determine the safety and pharmacokinetic profile of single oral doses of fluralaner at 10 mg/kg and 25 mg/kg in healthy adult horses.
• Subjects: 12 clinically healthy horses aged 9 to 17 years, university-owned, randomly assigned to either dosage group.
• Methods: Each horse received a single oral dose of fluralaner. A thorough monitoring protocol was followed over an 84-day period, including:
• Physical and neurological examinations to assess clinical safety.
• Blood sampling for plasma drug concentration, hematology, and biochemistry analysis.
• Skin biopsies to measure drug concentration in the skin over time.
• Fluralaner concentration was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and pharmacokinetic analysis was performed on plasma data.

Key Pharmacokinetic Findings

• Fluralaner was detected in plasma of all treated horses, showing effective oral absorption at both doses.
• Detection duration in plasma was:
• Approximately 42 ± 16.6 days for the 10 mg/kg dose.
• Approximately 30.3 ± 3.61 days for the 25 mg/kg dose.
• Pharmacokinetic parameters for 10 mg/kg and 25 mg/kg doses respectively:
• Terminal half-life: 6.03 ± 3.87 days (10 mg/kg), 3.02 ± 0.25 days (25 mg/kg).
• Maximum plasma concentration (Cmax): 162.1 ± 21.6 ng/mL (10 mg/kg), 403.3 ± 129.5 ng/mL (25 mg/kg).
• Time to maximum concentration (Tmax): 0.42 ± 0.14 days (10 mg/kg), 0.64 ± 0.29 days (25 mg/kg).
• Fluralaner concentrations in skin after the 25 mg/kg dose peaked at 2.30 μg/g (median) one day post-administration and remained detectable at day 84.

Safety and Tolerability

• No adverse reactions or toxic effects were reported during the 84-day study period for either dose group.
• Clinical assessments including physical and neurological exams showed no abnormalities attributable to fluralaner.
• Hematology and biochemistry panels remained within normal limits, supporting good tolerability of the drug.

Implications and Future Directions

• Oral fluralaner is effectively absorbed in horses and persists at measurable levels in plasma and skin, key tissues for controlling ectoparasites.
• The absence of adverse effects suggests fluralaner is safe for single-dose administration at the tested doses in healthy horses.
• Persistence of the drug in the skin for up to 84 days supports its potential utility as a long-lasting treatment against external parasites.
• Further research is necessary to establish optimal dosing regimens and intervals for effective parasite control and to evaluate efficacy against specific equine ectoparasites.
• Additional studies may also assess safety in broader horse populations and with repeated dosing schedules.