title: Pharmacokinetics of terbinafine after single oral dose administration in red-tailed hawks (Buteo jamaicensis).
abstract: 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 microg/mL, whereas a 30 mg/kg dose resulted in peak mean (+/- SD) plasma concentration of 1.2 +/- 0.40 microg/mL in 3 hours and a 60 mg/kg dose resulted in mean (+/- SD) concentration of 2.0 +/- 0.75 microg/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 microg/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.
authors.affiliation: College of Science, Oregon State University, 2082 Cordley Hall, Corvallis, OR 97331, USA.
authors.forename: Ursula
authors.initials: U
authors.lastname: Bechert
authors.forename: J Mark
authors.initials: JM
authors.lastname: Christensen
authors.forename: Robert
authors.initials: R
authors.lastname: Poppenga
authors.forename: Sahar A
authors.initials: SA
authors.lastname: Fahmy
authors.forename: Patrick
authors.initials: P
authors.lastname: Redig
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009281:Naphthalenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D020304:Raptors / Q000378:metabolism*; D000077291:Terbinafine; D014018:Tissue Distribution
chemical_list: D000935:Antifungal Agents; D009281:Naphthalenes; D000077291:Terbinafine