Comparison of the steady state pharmacokinetics of two formulations of cyclosporin in patients with atopic dermatitis

Abstract

A comparison was made of the efficacy, tolerability, safety and steady state pharmacokinetics of Sandimmun and Neoral in 11 stable atopic dermatitis patients already on Sandimmun. The study was of an open, crossover design. At entry into the trial, patients were switched to Neoral for 28 days. Treatment was switched back to Sandimmun for Days 28 to 42. The morning dose was given fasting, the evening dose after a standard meal. All measures of eczema severity improved during the Neoral treatment period. Neoral was markedly better tolerated with fewer side-effects. Switching from Sandimmun to Neoral at the same dose resulted in less variable pharmacokinetic profiles in both fasted and fed states. There was an increase in bioavailability with better, less variable and faster absorption, with a slightly reduced tmax, a higher mean Cmax (+43%) and a higher mean AUC (+30%) in fasted, but not fed patients. Higher trough levels (Cmin) occurred throughout for Neoral. These differences between the two formulations were not associated with any changes in safety parameters. Overall, Neoral was equivalent or superior to Sandimmun in tolerability and efficacy when given on a 1:1 dose basis.