Evaluation of persistence of terbinafine in the hair of normal cats after 14 days of daily therapy

Abstract

This study determined the residual concentration of terbinafine in cat hair after 14 days of oral treatment. Ten clinically normal cats were administered terbinafine orally at a daily dose of 34-45.7 mg kg(-1) for a total of 14 days. Areas of 15 cm(2) were shaved on the lateral thorax at day 0 and weekly for 8 weeks after the last dose of terbinafine. The hair samples were analysed by high-pressure liquid chromatography to determine the persistence of terbinafine over time. The mean terbinafine concentration in hair was 2.30 ng mg(-1) after 14 days of therapy. The half life was 1.84 weeks after the last dose of terbinafine. With a 99% confidence interval, the concentration of terbinafine remained in the cat hair at or above 0.03 ng mg(-1) (minimal inhibitory concentration (MIC)(90) = 0.03 microg mL(-1)) for 5.3 weeks. Slight deviations in the complete blood cell count and serum chemistry values were not attributed to terbinafine. Four cats experienced vomiting during the terbinafine treatment; two of these cats also experienced intense facial pruritus followed by a macular to papular skin reaction 7-14 days after the discontinuation of terbinafine. In summary, terbinafine persists in hair at concentrations above the MIC for several weeks after stopping medication, even after short-term therapy (14 days). These results suggest that pulse therapy of terbinafine should be further researched and potentially considered as a treatment modality for feline dermatophytosis, an approach that would decrease treatment duration while maintaining effectiveness.

Terbinafine pharmacokinetics after single dose oral administration in the dog

“…Therefore, the time to attain therapeutic concentrations in the hair follicle and stratum corneum may differ greatly from the time to achieve therapeutic concentrations in the plasma. Additionally, it is likely that in dogs, as has been demonstrated in humans and cats, terbinafine concentrations may persist in these tissues for a period of time after drug administration is discontinued 49,50 . This could potentially allow the use of a longer dosing interval or even pulsed dosing regimens when treating superficial dermatophytosis.…”

“…Studies in humans have shown that therapeutically significant concentrations of terbinafine are rapidly achieved in serum, skin and sebum with once daily oral dosing 49,51 . Additionally, a veterinary study demonstrated therapeutic concentrations of terbinafine in cat hairs after once daily oral dosing 50 . Future studies to examine alternative dosing protocols in dogs may be warranted.…”

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

“…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 topically applied terbinafine showed superior effectiveness in the treatment of experimental M. canis infection in guinea pigs (Ivaskiene et al 2011).…”

“…Allylamines and azoles are lipophilic drugs; they usually accumulate in the stratum corneum and hair follicles, and persist there at concentrations above the MIC for several weeks after a short-term therapy (Jessup et al 2000, Foust et al 2007). Absorption of lipophilic drugs into the bloodstream is very low after topical application (Schafer- Korting et al 2008).…”

Comparison of once‐daily versus twice‐weekly terbinafine administration for the treatment of canine Malassezia dermatitis – a pilot study

“…Although two recent studies in dogs have shown terbinafine to be well absorbed into the systemic circulation following oral administration, neither study evaluated the tissue distribution of terbinafine or its metabolites 12,13 . One possible explanation for why twice‐weekly dosing of terbinafine was effective in reducing MYC during treatment is that the drug is likely to concentrate in the sebum and keratinized structures of dogs, similar to that of humans and cats 17,35 . In humans, oral administration of terbinafine leads to rapid concentration of the drug in the stratum corneum and sebum, where elimination may be delayed for several days 8,17 .…”