Pharmacokinetics of Terbinafine in the Rabbit Ocular Tissues after Topical Administration

Abstract

Objective: To determine the distribution of terbinafine in the cornea and aqueous humor after topical administration. Methods: A corn oil ointment of terbinafine 0.2% (resolved in sterile corn oil) was applied to the conjunctival sac of albino rabbits twice (with a 5-min interval). The concentration of terbinafine was determined with high-performance liquid chromatography (HPLC) 5, 15, 30, 60, 120 and 240 min after administration of terbinafine. Results: After topical administration, the concentration of terbinafine increased gradually, reached a peak (1.39 µg/ml at 30 min in the cornea and 82.9 ng/ml at 30 min in aqueous humor, respectively) and then decreased. The concentration was 0.18 µg/g at 240 min in the cornea, but terbinafine could not be tested at 120 min in aqueous humor. Conclusions: Topical ophthalmic terbinafine 0.2% could penetrate into the cornea and aqueous humor at concentrations adequate for inhibition of fungus.

Positively Charged Polymeric Nanoparticle Reservoirs of Terbinafine Hydrochloride: Preclinical Implications for Controlled Drug Delivery in the Aqueous Humor of Rabbits

“…Based on the calculated AUC (0)(1)(2)(3)(4)(5)(6)(7)(8) values, the increase in the ocular bioavailability was found to be 1.657-fold. The drug penetration enhancement following the instillation of the NP suspension, could be related to colloidal carrier nature of NPs (nanosphere-mediated phenomenon) (47) as well as the appropriate drug lipophilicity (log P03.3).…”

“…At 5 min intervals, the loading of formulae was performed in two instillations using a micropipette. Care was taken to avoid touching the eye surface (8). At 0.5, 1, 2, 4, and 8 h post-instillation, the rabbits were locally anaesthetized (benoxinate HCl, 0.4% (w/v)) and aqueous humor samples (0.15 ml) were withdrawn by anterior chamber paracentesis (30)(31)(32).…”

“…However, the mean duration of treatment with T HCl was longer (7). Like natamycin, frequent instillation of T HCl drops once per 2 h at nighttime, once per hour in daytime, is necessary to maintain effective drug aqueous humor concentrations (8).…”

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

“…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.…”

“…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.…”