Cyclosporine bioequivalence study: quantification using fluorescence polarization immunoassay (FPIA) and radioimmunoassay (RIA)

Abstract

Objective: The aim of study was to compare the bioavailability of 2 cyclosporine capsule formulations (100 mg; Sigmasporin Microoral from Novaquímica Divisão Nature's Plus Farmacêutica Ltd., Brazil, as test formulation and Sandimmune Neoral from Novartis Biociências S.A., Brazil, as reference formulation) in 24 healthy male volunteers.

Methods: The study was open, randomized, with a 2-period crossover, a 1-week washout interval between doses. Blood samples were obtained over a 12-hour interval after each oral administration of cyclosporine (2 capsules of 100 mg of each formulation). Cyclosporine blood concentrations were quantified using a fluorescence polarization immunoassay (FPIA) method provided by Abbott Axsym System and Cyclo-Trac SP. Whole-blood radioimmuoassay (RIA) kit was provided by DiaSorin. These assays provided concentration-time curves for cyclosporine in blood concentration from which the following pharmacokinetic parameters were obtained: AUC(last), AUC(inf), Cmax.

Results: Geometric mean and 90% confidence intervals (CI) of Microoral/Neoral as percent ratios were 94.5% (90.8-98.4%) for AUC(last), 93.8% (89.7-98.1%) for AUC(inf), and 98.1% (94.5-101.8%) for Cmax when cyclosporine was determined using FPIA and 96.1% (91.9 to 100.6%) for AUC(last), 95.2% (90.2-100.5%) for AUC(inf), and 99.4% (96.4-102.4%) for Cmax using RIA.

Conclusion: Since the 90% CI for Cmax, AUC(last) and AUC(inf) ratio were within the 80-125% interval proposed by US-FDA, it is concluded that Sigmasporin Microoral 100 mg capsule formulation is bioequivalent to Sandimmune Neoral 100 mg capsule formulation with regard to both rate and the extent of absorption.