Comparison of two cyclosporine formulations in healthy Middle Eastern volunteers: bioequivalence of the new Sigmasporin Microoral and Sandimmun Neoral

A study was conducted to establish bioequivalence between two oral cyclosporine 100 mg capsules, Sigmasporin Microoral (Gulf Pharmaceutical Industries – Julphar, United Arab Emirates, under technical co-operation with Sigma Pharma, Brazil) and Sandimmun Neoral (Novartis, Switzerland), in a Middle Eastern population, even though both formulations were found to be bioequivalent earlier in a Brazilian population (data on file). It was designed as a randomized, open label, two-way crossover study in which 30 fasting, healthy male volunteers received a single 100 mg cyclosporine dose with 240 ml of water on two treatment days separated by a 1 week washout period. After dosing, serial blood samples were collected for a period of 24 h. Plasma was analyzed for cyclosporine A by a sensitive, reproducible and accurate HPLC method with MS detection capable of detecting cyclosporine A in the range of 5–400 ng/ml with a limit of quantitation of 5 ng/ml. Various pharmacokinetic parameters including AUC 0– t , AUC 0–∝, C max, T max, T 1/2, and λ Z were determined from plasma concentrations of both formulations. AUC 0– t , AUC 0–∝, and C max were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence intervals (82.98–110.57% for AUC 0– t , 81.57–124.71% for AUC 0–∝, 80.15–98.91% for C max) for these parameters were found to be within the bioequivalence acceptance range of 80–125%. Based on these statistical inferences, it was concluded that Sigmasporin Microoral ® is bioequivalent to Sandimmun Neoral ®.