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A new microemulsion formulation of cyclosporine was compared with the marketed formulation in 18 stable renal transplanted patients. Aim of the study was not only to determine the bioequivalence between the two pharmaceutical preparations, but also to ascertain whether tested drug could maintain stable blood concentrations of cyclosporine. Renal transplanted patients under cyclosporine treatment from at least 12 months at a well individualized dosage (resulting in 90-200 ng/mL of blood level drug) have been selected. Patients received the same preceding dose of cyclosporine through both the two preparations according to a cross-over, randomized schedule during 4 weeks in two equally divided daily administrations. Serial blood samples were obtained over a 24-hour period at steady-state of each formulation. Cyclosporine concentrations were determined by a specific immunoassay method (FPIA) n whole blood taken in the last day of each cycle of treatment. Statistical comparisons of cyclosporine levels (using pharmacokinetic parameters) were cross-performed between formulations and days of blood test. Tested drug resulted bioequivalent with the reference marketed formulation. Furthermore, the study showed that tested drug maintained satisfactory stable blood concentrations of cyclosporine.

This study evaluated the bioequivalence of a new Cyclosporine A microemulsion formulation in comparison to the reference market standard. Twenty-four adult healthy volunteers were randomised to receive the two Cyclosporin A microemulsion formulations, at a dose of 2.5 mg/kg, according to a cross-over design. Blood samples were taken before drug administration and at 12 points within 24 hours. Cyclosporine A whole blood concentrations were determined by HPLC. The pharmacokinetic parameters AUC0-t and AUC0-infinity were calculated by the trapezoidal rule, Cmax and Tmax were obtained directly from blood data. AUCs and Cmax were tested for bioequivalence after log transformation of data, differences for Tmax were evaluated by the rank test of Wilcoxon for paired data. The 90% confidence interval ratio between tested/reference drug was 0.98 for AUC0-t, 0.96 for AUC0-infinity and 1.01 for Cmax. All of them were within the range of bioequivalence. Tmax was 1.60 +/- 0.44 hours after test drug and 1.67 +/- 0.48 after reference drug (p = 0.27, Wilcoxon test). According to these results the two Cyclosporine A microemulsion formulations can be considered bioequivalent.