Effect of assay methodology on pharmacokinetic differences between cyclosporine Neoral and Sandimmune formulations.

ABSTRACT

The new oral formulation of cyclosporine (CsA), Neoral (CsA-N), results in increased area under the curve (AUC) and decreased intra- and interindividual variation in blood concentrations and other pharmacokinetic (PK) parameters when compared with the current Sand-immune (CsA-S) formulation. The present study examines the effect of assay methodology on variability in blood concentrations and PK parameters for renal transplant patients receiving CsA-N and CsA-S and whether this variation is reduced with CsA-N. The results show that interindividual variations in PK parameters for patients receiving CsA-N were less than those for patients receiving CsA-S. Both blood concentrations and dose of CsA better correlated with abbreviated (4-h) AUC after administration of CsA-N. For both CsA-S and CsA-N, blood concentrations at 4 h postdose exhibited the best correlation with AUC. All samples were analyzed by three common procedures HPLC, RIA, and fluorescence polarization immunoassay (FPIA). There were no significant differences observed in blood concentrations or PK parameters obtained from FPIA and RIA. HPLC results, however, were lower because of specificity of this method for the parent drug. The assay methodology did not have an effect on interindividual variability, indicating that the cross-reactivity of metabolites in commonly used immunoassays for CsA does not contribute to the PK variability observed in renal transplant patients.