title: Pharmacokinetics of orally administered terbinafine in African penguins (Spheniscus demersus) for potential treatment of aspergillosis.
abstract: The objective of this study was to determine the pharmacokinetic parameters of orally administered terbinafine hydrochloride based on 3, 7, and 15 mg/kg single- as well as multiple-dosage trials in order to calculate dosing requirements for potential treatment of aspergillosis in African penguins (Spheniscus demersus). Ten adult African penguins were used in each of these trials, with a 2-wk washout period between trials. Mean plasma concentrations of terbinafine peaked in approximately 4 hrs at 0.11 +/- 0.017 microg/ml (mean +/- SD) following administration of 3 mg/kg terbinafine, while 7 mg/kg and 15 mg/kg dosages resulted in peak plasma concentrations of 0.37 +/- 0.105 and 0.33 +/- 0.054 microg/ml, respectively. The volume of distribution increased with increasing dosages, being 37 +/- 28.5, 40 +/- 28.1, and 52 +/- 18.6 mg/L for 3, 7, and 15 mg/kg doses, respectively. The mean half-life was biphasic with initial terminal half-life (t(1/2)) values of 9.9 +/- 4.5, 17.2 +/- 4.9 and 16.9 +/- 5.4 hrs, for 3, 7, and 15 mg/kg doses, respectively. A rapid first elimination phase was followed by a slower second phase, and final elimination was estimated to be 136 +/- 9.7 and 131 +/- 9.9 hrs, for 7 and 15 mg/kg doses, respectively. Linearity was demonstrated for area under the curve but not for peak plasma concentrations for the three dosages used. Calculations based on pharmacokinetic parameter values indicate that a 15 mg/kg terbinafine q24h dosage regimen would result in steady-state trough plasma concentrations above the minimum inhibitory concentration (0.8-1.6 microg/ ml), and this dosage is recommended as a potential treatment option for aspergillosis in penguins. However, additional research is required to determine both treatment efficacy and safety.
authors.affiliation: Oregon State University, College of Science, 2082 Cordley Hall, Corvallis, Oregon 97331, USA. ursula.bechert@oregonstate.edu
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: Hang
authors.initials: H
authors.lastname: Le
authors.forename: Jeff
authors.initials: J
authors.lastname: Wyatt
authors.forename: Todd
authors.initials: T
authors.lastname: Schmitt
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001228:Aspergillosis / Q000188:drug therapy / Q000662:veterinary*; D001715:Bird Diseases / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D008297:Male; D015394:Molecular Structure; D009281:Naphthalenes / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D046429:Spheniscidae; D000077291:Terbinafine
chemical_list: D000935:Antifungal Agents; D009281:Naphthalenes; D000077291:Terbinafine