Terbinafine pharmacokinetics after single dose oral administration in the dog

Abstract

Terbinafine is an allylamine antifungal prescribed for the treatment of mycoses in humans. It is increasingly being used in veterinary patients. The purpose of this study was to evaluate the pharmacokinetic properties of terbinafine in dogs after a single oral dose. Ten healthy adult dogs were included in the study. A single dose of terbinafine (30-35 mg/kg) was administered orally, and blood samples were periodically collected over a 24 h period during which dogs were monitored for adverse effects. Two of 10 dogs developed transient ocular changes. A high-performance liquid chromatography assay was developed and used to determine plasma terbinafine concentrations. Pharmacokinetic analysis was performed using PK Solutions(®) computer software. Area under the curve (AUC) from time 0 to 24 h was 15.4 μg·h/mL (range 5-27), maximal plasma concentration (C(max) ) was 3.5 μg/mL (range 3-4.9 μg/mL) and time to C(max) (T(max) ) was 3.6 h (range 2-6 h). The time above minimal inhibitory concentration (T > MIC) as well as AUC/MIC was calculated for important invasive fungal pathogens and dermatophytes. The T > MIC was 17-18 h for Blastomyces dermatitidis, Histoplasma capsulatum and dermatophytes (Microsporum spp. and Trichophyton mentagrophytes), while the MIC for Sporothrix schenckii and Coccidioides immitis was exceeded for 9.5-11 h. The AUC/MIC values ranged from 9 to 13 μg h/mL for these fungi. Our results provide evidence supporting the use of terbinafine as an oral therapeutic agent for treating systemic and subcutaneous mycoses in dogs.

Clinical, Morphological, and Molecular Characterization of Penicilliumcanissp. nov., Isolated from a Dog with Osteomyelitis

“…It is well recognized that combination antifungal therapy has potential synergistic effects (40)(41)(42)(43). Furthermore, the MICs of both drugs were suggestive of drug efficacy, as these concentrations should be readily achieved on the basis of canine pharmacokinetic studies (44,45). Clinical and radiographic improvements observed in the dog in our report substantiated the efficacy of this multimodal therapy.…”

Prototheca wickerhamii in a dog with cutaneous, ocular and systemic manifestations and treatment with terbinafine

“…Terbinafine dosing in dogs for superficial and deep mycoses is recommended at 20–40 mg/kg every 12–24 hours (Williams and others 2010, Sakai and others 2011, Ramsey 2012, Miller and others 2013, Plumb 2015). In this case, a dose of 29.5 mg/kg every 24 hours was chosen.…”

Efficacy of Topical Therapy with Newly Developed Terbinafine and Econazole Formulations in the Treatment of Dermatophytosis in Cats

“…Over the past decade, the effectiveness and tolerability of terbinafine were actively investigated in the treatment of animal dermatomycoses (Bechert et al 2010, Sakai et al 2011, Williams et al 2011, Wang et al 2012. After a number of studies in animals, scientists have proved that orally administered terbinafine is effective in the treatment of cats suffering from experimentally induced or naturally occurring dermatophytosis (Castanon-Olivares et al 2001, Kotnik 2002, Kotnik and Cerne 2006, Foust et al 2007).…”

“…Recently, econazole and terbinafine are widely used in antifungal preparations for human mycoses, however these agents are not licensed for use in animals. Although terbinafine is prescribed for the treatment of mycoses in humans, it is increasingly being used in veterinary patients (Sakai et al 2011). In Lithuania, available topical formulations for use in pets are Surolan ® , Malaseb ® (miconazole) and Imaverol ® (enilconazole), which contain antifungals of first generation imidazole, that are fungistatic, have narrow spectrum of activity and the development of resistance to these antifungals has become increasingly apparent.…”