Influence of food intake on the clinical response to cyclosporin A in canine atopic dermatitis

CYCLOSPORIN A (CsA) (Atopica, Atoplus soft capsules; Novartis Animal Health) was introduced recently as an oral microemulsion formulation for the treatment of dogs with atopic dermatitis. Several randomised, controlled and open clinical studies have proven its clinical efficacy (Olivry and others 2002, Steffan and others 2003, 2004). Based on pharmacokinetic data, administration of CsA is recommended two hours before or after feeding, as its bioavailability decreases and the variability of individual blood concentrations increases when the drug is given with food (Steffan and others 2004). Dosing fasted dogs is therefore recommended to optimise the drug’s bioavailability. However, the clinical response of dogs after dosing with or without food has never been evaluated. This short communication describes a study to determine whether the administration of CsA with or without food could influence the clinical response in dogs with atopic dermatitis. Twenty-five dogs with non-seasonal atopic dermatitis, diagnosed by Prelaud’s criteria (Prelaud and others 1998) and by exclusion of differential diagnoses, were included in a multicentre, randomised study involving seven investigators in Germany. All the dogs received approximately 5 mg/kg/day CsA. The animals were randomly and sequentially divided into two groups by the lead investigator, independent of the study centre, alternating between group 1 and 2. As the various centres included dogs at different time points, the number of dogs in each group was not identical at each centre. The 15 dogs in group 1 received CsA with a meal, while the 10 dogs in group 2 were given the drug at least two hours before or after feeding. Dogs were evaluated before treatment and monthly for six months thereafter. A dose tapering regimen was applied, as described by Steffan and others (2003). The canine atopic dermatitis extent and severity index (CADESI), with scores of 0 to 3 for erythema, lichenification and ex coriation at 40 different body sites, was used by the clinician at each centre, as previously described by Olivry and others (2002); pruritus was evaluated by the owner, using a visual analogue scale from 0 to 100. If the CADESI score increased above baseline, the dog was excluded from the study. If the CADESI score at any given visit was reduced by more than 50 per cent and the pruritus was adequately controlled, administration of CsA was reduced to every second day of treatment. If the CADESI score had improved by more than 75 per cent from baseline and pruritus was well controlled, the drug was administered twice weekly. If, on subsequent visits, the CADESI scores or pruritus increased, the frequency of administration was increased again to the previous level. During a selection period of four weeks, all the dogs were treated with a long-lasting flea adulticide spot-on formulation such as selamectin, imidacloprid, fipronil or permethrin. Fipronil was used monthly during the study. Systemic antibiotics and antifungal drugs were administered as required for the treatment of secondary infections. Antipruritic drugs had to be withdrawn before inclusion in the study (CsA for eight weeks, injectable glucocorticoids for four weeks, oral/ topical glucocorticoids for one week and allergen-specific immunotherapy for two weeks). Fatty acid supplementation Veterinary Record (2006) 159, 854-856