Single dose pharmacokinetics of terbinafine in cats

Abstract

The pharmacokinetics of terbinafine was studied in six healthy fasted cats following a single intravenous and oral administration at a dose of 10 mg/kg and 30 mg/kg, respectively, according to a two-period crossover design. Plasma terbinafine concentrations were determined using a reverse phase liquid chromatographic method. The pharmacokinetic parameters were calculated by non-compartmental analysis with WinNonlin 5.2.1 software. After intravenous administration, the terminal half-life and area under the curve from time 0 to infinity were 10.40 ± 4.56 h, 15.20 ± 3.61 h·µg/ml, respectively. After oral dosing, the mean maximum concentration was 3.22 ± 0.60 µg/ml, reached at 1.33 ± 0.41 h. The terminal half-life, area under the curve from time 0 to infinity and apparent volume of distribution were 8.01 ± 3.46 h, 13.77 ± 4.99 h·µg/ml, 25.63 ± 6.29 l/kg, respectively. The absolute bioavailability of terbinafine hydrochloride tablets after oral administration was 31.00 ± 10.85%. Although bioavailability was low, excellent penetration at the site of infection and low minimum inhibitory concentrations values provided terbinafine with good efficacy against dermatophyte infections.

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).…”

Pharmacokinetics of nebulized and subcutaneously implanted terbinafine in cottonmouths (Agkistrodon piscivorus)

“…These data were used to determine the target plasma concentrations for terbinafine in the pharmacokinetic studies. Data on the establishment of MIC for antifungal medications are variable and commonly utilize in vitro susceptibility as a starting point (Gimmler, White, Kennis, Cruz‐Espindola, & Booth, ; Orosz et al., ; Wang et al., ) unlike quantitative methods used for antibiotics (AUC/MIC or C max /MIC). However, if we utilized the conventional antibiotic predictive methods, the therapeutic concentrations determined by AUC/MIC (88 ng/ml) and C max /MIC (15.4 ng/ml) are above the plasma concentrations we detected.…”

“…Terbinafine has been administered to canines, lagomorphs, felines, and avian species via a variety of routes including those not evaluated in this study: intravenous, oral, and topical (Bechert, Christensen, Poppenga, Le et al., ; Bechert, Christensen, Poppenga, Fahmy, & Redig, ; Evans et al., ; Hosseini‐Yeganeh and McLachlan, ; Sakai et al., ; Sun et al., ; Wang et al., ; Williams et al., ). Oral administration is less practical for the treatment of snakes as these animals feed bimonthly and administration is more challenging in venomous species.…”

“…Terbinafine inhibits squalene epoxidase, an enzyme involved in ergosterol synthesis, which interferes with membrane function and cell growth causing fungistatic activity. (Birnbaum, 1990;Ryder & Favre, 1997;Wang, Ding, Liu, Gao, & Zeng, 2012).…”

“…Pharmacokinetic studies for terbinafine hydrochloride have previously been documented in birds, horses, dogs, cats, rabbits, and rats (Bechert, Christensen, Poppenga, Le et al, 2010;Bechert, Christensen, Poppenga, Fahmy, & Redig, 2010;Emery, Cox, & Souza, 2012;Evans, Emery, Cox, & Souza, 2013;Hosseini-Yeganeh and McLachlan, 2001;Sakai et al, 2011;Sun et al, 2007;Wang et al, 2012;Williams, Davis, & KuKanich, 2010). However, antifungal pharmacokinetics studies in squamates are limited (Brosnan, Pypendop, Barter, & Hawkins, 2006;Churgin, Musgrave, Cox, & Sladky, 2014;Gamble, Alvarado, & Bennett, 1997;Tuttle et al, 2006;Van Waeyenberghe et al, 2010), and those involving terbinafine are nonexistent.…”