Comparison of predose vs 2-h postdose blood metabolites/cyclosporine ratios in kidney and liver transplant patients

Objectives: It has recently been suggested that when adjusting doses of cyclosporine (CsA), determining its concentration in blood samples taken 2 h postdose (C2) is more clinically beneficial than using the predose concentration (C0). We determined C0 and C2 concentrations of CsA and their metabolites in samples taken from nine kidney and seven liver transplant patients. Similarly, the so-called metabolic ratios (MR)—metabolites to CsA parent ratios—were calculated to characterise the most suitable moment of blood sampling for obtaining a greater analytical specificity with monoclonal immunoassays. Methods: The determination of CsA and CsA + metabolites was made using the enzyme multiplied immunotechnique and the polyclonal fluorescence polarization immunoassay Abbott TDx, respectively. Results: The poor correlation between C0 and C2 of CsA (n = 82, r = 0.387, p< 0.001) is greatly inferior to that obtained between C0 and C2 of metabolites (n = 82, r = 0.912, p< 0.001). A highly significant difference (p< 0.001) was found between MR0 values (mean 2.87 ± 0.12, median 2.48) and MR2 values (mean 1.73 ± 0.09, median 1.46), although there is a good correlation between them (r = 0.878, p< 0.001). Conclusions: The extent of the positive bias (deviation) of CsA immunoassays compared with the high-performance liquid chromatography results is related to the MR values. As the MR2 values are significantly lower than the corresponding MR0, in practice a greater analytical specificity would be obtained with the different monoclonal immunoassays in the determination of the 2 h postdose CsA concentration than in that of trough concentration.