Comparison of whole blood concentrations of oral human generic modified ciclosporin capsules with microemulsified ciclosporin capsules approved for canine atopic dermatitis following a single oral administration to healthy dogs.

Abstract

BACKGROUND: There have been no comparative bioavailability studies between the microemulsified ciclosporin formulation, approved for the treatment of canine atopic dermatitis (cAD), and the generic modified formulation of ciclosporin for humans. OBJECTIVES: To compare whole blood ciclosporin concentrations of oral generic modified ciclosporin (Treatment A; Teva Pharmaceuticals) and ciclosporin brand Atopica (Treatment B; Elanco Animal Health) in healthy dogs at 1 and 1.5 h following a single oral administration. METHODS: Whole blood concentrations were evaluated at 1 and 1.5 h post-oral administration of treatments A and B in a randomised, blinded, cross-over study with an 8-day wash-out, after a single administration at 4.4-5.3 mg/kg/day in eight healthy, male-castrated research beagle dogs. Ciclosporin blood concentrations were measured through the Auburn University Clinical Pharmacology Laboratory. RESULTS: Ciclosporin blood concentrations were below the detection limit before the start of treatment for both groups. Blood ciclosporin concentrations for Treatment A (median 1192 ng/ml) were significantly higher at 1 h post-oral administration than those for Treatment B (median 499 ng/ml; p = 0.001). However, no significant differences (p = 0.75) in ciclosporin values were observed at 1.5 h post-administration between treatments A (median 945 ng/ml) and B (median 809 ng/ml). CONCLUSIONS AND CLINICAL RELEVANCE: Generic modified ciclosporin achieved higher blood concentrations at 1 h post-administration than Atopica after a single oral administration in healthy dogs; no difference was noted at 1.5 h. Further clinical studies using generic modified ciclosporin in client-owned dogs affected with cAD are advocated to confirm its therapeutic efficacy.