Comparison of cyclosporin A pharmacokinetics of a new microemulsion formulation and standard oral preparation in patients with psoriasis

Abstract

Cyclosporin A (CyA) is a potent immunosuppressive drug which has shown efficacy in various skin disorders. The bioavailability of the oral CyA formulation (Sandimmun) is approximately 30%, showing high interpatient and intrapatient variability. The steady-state pharmacokinetics, efficacy and tolerability of CyA in two formulations: commercial Sandimmun soft gelatin capsules (CyA-SGC) and a newer oral formulation (Sandimmun Neoral: CyA-NOF), were compared in an open prospective study with a crossover between the two treatments in 19 patients with psoriasis. Each patient received a twice-daily treatment of CyA with a clinically effective dose of 2-5 mg/kg per day. The individual dosages were kept unchanged for at least 2 weeks before study entry and over the 42-day course of the study. At entry, patients were switched to CyA-NOF for 4 weeks and then back to CyA-SGC for another 2 weeks. Pharmacokinetic profiles were assessed at steady-state on day 14 while the patients were on CyA-NOF, and on day 42 while on CyA-SGC. Switching from CyA-SGC to CyA-NOF using 1:1 dose conversion resulted in an increased absorption of the drug. On average there was a 61% increase in maximum drug concentration (Cmax) and a 32% increase in the area under the steady-state blood concentration-time curve (AUC): Cmin was comparable in the two formulations. The increases in Cmax and AUC were associated with some increase in the clinical efficacy of the treatment. The number of adverse events reported by the patients and observed by the investigators were increased during CyA-NOF; the mean serum creatinine levels were not affected. An increased and a more consistent and predictable absorption of CyA is achieved with the new oral microemulsion formulation.