Pharmacokinetic and pharmacodynamic evaluation of cyclosporin A O/W-emulsion in rats

The pharmacokinetics and pharmacodynamics of the cyclosporin A (CSA) O/W-emulsion were studied after intravenous and oral administration to Sprague-Dawley rats. Two commercial products, CIPOL Inj.(R) and Sandimmun Neoral(R), were used as the reference formulations. CSA concentration and lymphocyte populations in whole blood were measured by TDxFLx(R) and Coulter STKS(R), respectively. The pharmacokinetic and pharmacodynamic parameters were obtained by fitting experimental data to two-compartment model and to indirect pharmacodynamic model, respectively, using WINNONLIN. The area under the concentration-time curve (AUC), terminal half-lives (T-1/2), total clearance (CLt) and relative bioavailability (F) after intravenous administration of CSA O/W-emulsion were not significantly different from those of intravenous administration of CIPOL Inj.(R) (P > 0.05). In oral administration, AUC and C-max of CSA O/W-emulsion were significantly decreased (P < 0.05), while T-1/2, MRT, T a and F were not significantly different (P > 0.05) from those of Sandimmun Neoral(R). However, the area between the baseline and effect curves (ABEC) and pharmacodynamic efficiency (EFF) of CSA O/W-emulsion were significantly greater than those of references regardless of routes of administration (P < 0.05). The pharmacodynamic availability (F-PD) of CSA O/W-emulsion was 1.79- and 2.13-fold higher than that of CIPOL Inj.(R) and Sandimmun Neroal(R) (P < 0.05), respectively. (C) 2002 Elsevier Science B.V. All rights reserved.