Single-dose pharmacokinetics of orally administered terbinafine in bearded dragons (Pogona vitticeps) and the antifungal susceptibility patterns of Nannizziopsis guarroi

Abstract

OBJECTIVE To identify the antifungal susceptibility of Nanniziopsis guarroi isolates and to evaluate the single-dose pharmacokinetics of orally administered terbinafine in bearded dragons. ANIMALS 8 healthy adult bearded dragons. PROCEDURES 4 isolates of N guarroi were tested for antifungal susceptibility. A compounded oral solution of terbinafine (25 mg/mL [20 mg/kg]) was given before blood (0.2 mL) was drawn from the ventral tail vein at 0, 4, 8, 12, 24, 48, 72, and 96 hours after administration. Plasma terbinafine concentrations were measured with high-performance liquid chromatography. RESULTS The antifungal minimum inhibitory concentrations against N guarroi isolates ranged from 4,000 to > 64,000 ng/mL for fluconazole, 125 to 2,000 ng/mL for itraconazole, 125 to 2,000 ng/mL for ketoconazole, 125 to 1,000 ng/mL for posaconazole, 60 to 250 ng/mL for voriconazole, and 15 to 30 ng/mL for terbinafine. The mean ± SD peak plasma terbinafine concentration in bearded dragons was 435 ± 338 ng/mL at 13 ± 4.66 hours after administration. Plasma concentrations remained > 30 ng/mL for > 24 hours in all bearded dragons and for > 48 hours in 6 of 8 bearded dragons. Mean ± SD terminal half-life following oral administration was 21.2 ± 12.40 hours. CLINICAL RELEVANCE Antifungal susceptibility data are available for use in clinical decision making. Results indicated that administration of terbinafine (20 mg/kg, PO, q 24 to 48 h) in bearded dragons may be appropriate for the treatment of dermatomycoses caused by N guarroi. Clinical studies are needed to determine the efficacy of such treatment.

Bioencapsulation is a feasible method of terbinafine administration in Emydomyces testavorans-infected western pond turtles (Actinemys marmorata)

“…In bearded dragons, females had higher plasma terbinafine concentrations than males, suspected to be due to higher volumes of distribution from seasonal plasma protein fluctuations from vitellogenesis. 33 In the current study, all turtles had unremarkable complete blood count, serum biochemistry, and protein electrophoresis results. Further research is necessary to assess for potential differences in terbinafine pharmacokinetics between males and females.…”

“…The T max of terbinafine given via OG was similar to that of red-eared sliders (Trachemys scripta elegans, 1.3 hours), cats (Felis catus, 1.3 hours), horses (Equus ferus caballus, 1.7 hours), and dogs (Canis lupus familiaris, 2.0 hours) but faster than that of red-tailed hawks (Buteo jamaicensis, 3.4 hours), African penguins (Spheniscus demersus, 4.0 hours), Hispaniolan amazon parrots (Amazona ventralis, 6.4 hours), and bearded dragons (Pogona vitticeps,13.0 hours). [29][30][31][32][33][34][35] Given the small sample size of this study, the study was likely underpowered to detect statistical differences. The difference in T max between the administration groups (BEC and OG) was not statistically significant (P = .062), and administration of terbinafine via BEC reached maximal plasma concentration at 14.1 hours on average compared to 1.8 hours in the OG group.…”

“…These concentrations were greater than that of bearded dragons and horses administered a 20-mg/kg dose (434 and 310 ng/ mL, respectively), red eared sliders, and African penguins receiving a 15-mg/kg dose (201 and 200 ng/mL, respectively), Hispaniolan amazon parrots receiving a 60-mg/kg dose (353 ng/mL), and western pond turtles administered an 18-mg dose (27 to 91 mg/kg) via nebulization (no plasma levels detected). [30][31][32][33]35,36 The greater Cmax in western pond turtles may be due to species differences in absorption, potentially secondary to gastrointestinal environment, terbinafine solubility, or delayed metabolism given their slower overall metabolic rate. However, both routes of administration resulted…”

“…[30][31][32]35 BEC administration in western pond turtles demonstrated a greater AUC/ dose than cats, dogs, red-tailed hawks, and bearded dragons (459 ng X h X kg X mL −1 /dose rate, 575 ng X h X kg X mL −1 /dose rate, 588 ng X h X kg X mL −1 / dose rate, and 758 ng X h X kg X mL −1 /dose rate, respectively). 29,[33][34][35] In order for direct comparison of OG to the BEC phase, turtles that were administered terbinafine via oral gavage were fed an earthworm immediately following terbinafine administration; thus, the differences in AUC between routes are not simply due to the presence of food and changes in gastrointestinal transit time. In red-tailed hawks, terbinafine absorption was unaffected when administered with food; however, in humans, a greater C max was achieved when terbinafine was administered with a meal.…”

“…Half-life was similar between OG (26.2 hours) and BEC (27 hours) administration and similar to that of the bearded dragon (21.2 hours), African penguin (17.0 hours), and red-tailed hawk (17.5 hours) but longer than that of the red-eared slider (5.4 hours), cat (8.01 hours), dog (8.6 hours), horse (8.1 hours), and Amazon parrot (8.7 hours). [29][30][31][32][33][34][35] The keratinophilic and lipophilic nature of terbinafine in theory may influence half-life by accumulating in keratinized tissues such as the shell, which could result in a large volume of distribution. 36 Furthermore, while data on the protein affinity of terbinafine in reptiles are unknown, in domestic species, terbinafine is highly protein bound.…”