Pharmacokinetics of Orally Administered Terbinafine in African Penguins (Spheniscus demersus) for Potential Treatment of Aspergillosis

• Published in: Journal of zoo and wildlife medicine 2010-06, Vol.41 (2), p.263-274
• Main Authors: Bechert, Ursula, Christensen, J. Mark, Poppenga, Robert, Le, Hang, Wyatt, Jeff, Schmitt, Todd
• Format: Article
• Language: English
• Subjects: African penguins; Animals; Antifungal Agents - blood; Antifungal Agents - chemistry; Antifungal Agents - pharmacokinetics; Antifungal Agents - therapeutic use; Antifungals; Area Under Curve; Aspergillosis; Aspergillosis - drug therapy; Aspergillosis - veterinary; Aspergillus; Bird Diseases - drug therapy; Blood plasma; Dosage; Dose-Response Relationship, Drug; Experimentation; Female; Half-Life; Infections; Male; Marine; Molecular Structure; Naphthalenes - blood; Naphthalenes - chemistry; Naphthalenes - pharmacokinetics; Naphthalenes - therapeutic use; Penguins; Pharmacokinetics; REVIEW ARTICLES; s; Spheniscidae; Spheniscus demersus; Terbinafine; Zoos
• ISSN: 1042-7260; 1937-2825
• DOI: 10.1638/2009-0211R.1

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 µg/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 µg/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 (t½) 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 µg/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.