Pharmacokinetics of terbinafine after single oral dose administration in red-tailed hawks (Buteo jamaicensis)

To determine pharmacokinetic parameters of orally administered terbinafine hydrochloride for potential treatment of aspergillosis in raptors, 10 adult red-tailed hawks (Buteo jamaicensis) were used in single dose trials by using 15, 30, and 60 mg/kg doses with a 2-week washout period between trials. After administration of 15 mg/kg terbinafine, mean (± SD) plasma concentration peaked in approximately 5 hours at 0.3 ± 0.24 μg/mL, whereas a 30 mg/kg dose resulted in peak mean (± SD) plasma concentration of 1.2 ± 0.40 μg/mL in 3 hours and a 60 mg/kg dose resulted in mean (± SD) concentration of 2.0 ± 0.75 μg/mL in 5 hours. The volume of distribution decreased with increasing doses, averaging 76.8 ± 38.06 mL/kg for the 15 mg/kg dose and falling to 55.2 ± 17.4 mL/kg for the 30 mg/kg dose. This suggests that terbinafine accumulated in deep tissues, limiting further distribution at higher doses. The harmonic mean (± SD) half-life was biphasic, with initial values of 14.7 ± 6.67 hours, 17.5 ± 8.7 hours, and 13.3 ± 5.03 hours for 15, 30, and 60 mg/kg doses, respectively. A rapid first-elimination phase was followed by a slower second phase, and final elimination was estimated to be 161 ± 78.2 and 147 ± 65.6 hours for 15 and 30 mg/kg doses, respectively. Linearity was demonstrated for the area under the curve but not for peak plasma concentrations for the 3 doses used. Calculations based on pharmacokinetic parameter values indicated that a dosage of 22 mg/kg terbinafine q24h would result in steady-state trough plasma concentrations above the minimum inhibitory concentration of terbinafine (0.8-1.6 μg/mL). This dosage is recommended as a potential treatment option for aspergillosis in raptors. However, additional research is required to determine both treatment efficacy and safety.