Determining canine skin concentrations of terbinafine to guide the treatment of Malassezia dermatitis.

Abstract

Terbinafine (TBF) is known to concentrate and persist in human skin. Its use is increasing in veterinary medicine, but there are limited data concerning its tissue concentration and efficacy in dogs. (i) Describe TBF accumulation in canine skin; (ii) Integrate pharmacokinetic data with historical minimum inhibitory concentration (MIC) results for Malassezia pachydermatis to verify the currently used dosage of TBF for the treatment of Malassezia dermatitis. Ten healthy, client-owned dogs. Dogs were given TBF (generic preparation, 250 mg tablets) 30 mg/kg per os (p.o.) once daily for 21 days. Serum, sebum and stratum corneum (SC) samples were collected on days 1, 5, 7, 11, 14, 21, 28 and 35. High-pressure liquid chromatography was used to determine drug concentrations in samples. Relevant (mean ± standard deviation) parameters for TBF in serum, paw SC, thorax SC and sebum, respectively, were: maximum concentration (Cmax , μg/mL) 23.59 ± 10.41, 0.31 ± 0.26, 0.30 ± 0.32 and 0.48 ± 0.25; half-life (t1/2 , d) 4.49 ± 2.24, 6.34 ± 5.33, 4.64 ± 3.27 and 5.12 ± 3.33; time to maximum concentration (Tmax , d) 10.40 ± 6.98, 13.20 ± 5.16, 11.90 ± 8.62 and 10.60 ± 3.69. These results suggest that TBF does not achieve high concentrations in canine SC or sebum compared to serum. The mean Cmax of all skin tissues (paw SC, thorax SC and sebum) barely exceeded the reported Malassezia MIC90, of 0.25 μg/mL, which indicates that doses higher than 30 mg/kg p.o. once daily may be necessary.