Efficacy and Pharmacokinetics of Two Formulations of Cyclosporine A in Patients with Psoriasis

Abstract

The efficacy and pharmacokinetic profiles of two oral formulations of cyclosporine A (Sandimmune and Neoral; Sandoz Pharmaceuticals, East Hanover, NJ) were evaluated in 37 patients with moderate to severe plaque psoriasis in a randomized, double-blind, modified, crossover study. Cyclosporine A (150 mg twice daily), administered in either formulation, reduced the severity of plaque lesions: 94% of all patients reported at least moderate improvement and 70% reported complete clearing. Approximately 2 weeks of therapy were required for drug exposure to stabilize on either formulation. Cyclosporine A exposure from Neoral was significantly greater relative to that from Sandimmune across all study weeks. At the eighth week (before crossover), AUC and Cmax values for Neoral and Sandimmune were 5618 +/- 1705 versus 3202 +/- 596 ng.h/mL and 1283 +/- 337 versus 623 +/- 173 ng/mL, respectively. In crossover analysis at steady state, the relative oral bioavailability of cyclosporine from the Neoral formulation was 54% greater than that from Sandimmune. Some pharmacokinetic parameters showed less variability both between and within groups of patients taking Neoral versus Sandimmune. Both formulations were well tolerated, in that most adverse events were of mild severity.

Comparison of Two Formulations of Cyclosporin A in the Treatment of Severe Atopic Dermatitis

“…This was not the case in the group treated with Sandimmun. The time course of the improvement of the patients’ condition under Neoral in this study faithfully mirrors the rapid increase of trough concentration measured by Elder et al [10]. One may thus hypothesise that the faster onset of action of Neoral might be related to its better pharmacokinetic profile.…”

“…A possible explanation for the faster onset of action of Neoral is provided by the data of Elder et al [10]. After 8 weeks of treatment with 300 mg CsA per day, a dosage comparable to that used in this study, the average trough concentrations were significantly higher in the group treated with Neoral compared to the group treated with Sandimmun.…”

“…Unfortunately, the use of CsA (Sandimmun ® ) has been hampered by high inter- and intrapatient variability in its bioavailability [9, 10]and dose-dependent side effects [11]. The use of CsA as a microemulsion [12](Sandimmun Neoral ® : Neoral) in the treatment of dermatological diseases was pioneered by Bourke et al [13].…”

“…The use of CsA as a microemulsion [12](Sandimmun Neoral ® : Neoral) in the treatment of dermatological diseases was pioneered by Bourke et al [13]. Further investigations showed that the use of Neoral yielded more reproducible pharmacokinetic properties resulting in improved control of therapy and fewer adverse events [9, 10]. …”

Single-Dose and Steady State Pharmacokinetics of Csa and Two Main Primary Metabolites, Am1 and Am4n in Patients With Rheumatic/Autoimmune Diseases

“…Data describing the pharmacokinetics of CsA in autoimmune diseases however are relatively rare. Few data are available for patients with rheumatoid arthritis [30][31][32] , but more consistent data were found for psoriasis treatment [33][34][35][36][37] . None of these studies however described the pharmacokinetics of the main primary CsA metabolites AM1 and AM4N.…”