Increased bioavailability and improved efficacy, in severe psoriasis, of a new microemulsion formulation of cyclosporin

Abstract

Cyclosporin, as the microemulsion formulation Neoral, was given to two groups of patients with severe psoriasis (Psoriasis Area and Severity Index: PASI > 12.0). Group A (10 patients) were receiving the traditional formulation of cyclosporin, Sandimmun, at the start of the study, with a partial clinical response, and were switched to Neoral at the same dose (3.3 mg/kg per day). Group B patients, who had previously been treated with Sandimmun but were treatment failures, were given Neoral, 3.5 mg/kg per day. This led to rapid improvement in psoriasis in both groups. In Group A mean PASI fell from 22.3 to 11.6 on Sandimmun, after 82 +/- 30 weeks, and to 4.0 (P < 0.05) after 32 weeks of Neoral. In Group B mean PASI decreased from 20.3 to 3.7 (P < 0.05) at a dose of 3.1 mg/kg per day. Pharmacokinetic data demonstrated significant decrease in tmax from 2.3 to 1.4 hours. After 2 weeks Cmax and the area under the curve (AUC) (0-4 h) were significantly increased by 41% and 61%, respectively. Further pharmacokinetic data at 3 months showed similar results. No significant changes in renal function from pre-treatment status were seen in either group. None of the patients developed hypertension. No serious adverse events were reported. The microemulsion formulation of cyclosporin showed greater efficacy and bioavailability. Improved outcome was seen at doses which were on average 15% lower than with the traditional formulation, leading to a reduction in cost of treatment.