The effect of ketoconazole on whole blood and skin ciclosporin concentrations in dogs

Background –  Ciclosporin (CSA) is approved for the treatment of canine atopic dermatitis. Ciclosporin is metabolized by liver cytochrome P450 enzymes, a process inhibited by ketoconazole (KTZ). Hypothesis/Objectives –  The aims of this study were to determine skin and blood CSA concentrations when CSA was administered alone at 5.0 (Treatment 1) or 2.5 mg/kg (Treatment 2) and when CSA was administered at 2.5 mg/kg concurrently with KTZ at 5 (Treatment 3) or 2.5 mg/kg (Treatment 4). We hypothesized that skin and blood CSA concentrations in Treatment 1 would not differ from those obtained with T3 or T4. Animals –  In a randomized cross‐over study, six healthy research dogs received each of the treatments (Treatment 1, 2, 3 and 4) once daily for 7 days. Methods –  After the first, fourth and seventh dose for each treatment, a peak and trough skin punch biopsy sample and whole blood sample were collected and analysed with high‐performance liquid chromatography–tandem mass spectrometry. Data were analysed using a repeated measures approach with PROC MIXED in SAS. Pairwise comparisons were performed with least squares means and Tukey–Kramer adjustment for multiple comparisons. Results –  Mean blood CSA concentrations in Treatment 1 were not different from those in Treatment 2 or 4, but were less than in Treatment 3. Mean skin CSA concentrations in Treatment 1 were greater than in Treatment 2, not different from those in Treatment 4, and less than those in Treatment 3. Conclusions and clinical importance –  Administration of CSA and KTZ concurrently at 2.5 mg/kg each may be as effective as CSA alone at 5.0 mg/kg for treatment of canine atopic dermatitis.