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 (C-2) is more clinically beneficial than using the predose concentration (C-0). We determined C-0 and C-2 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 C-0 and C-2 of CsA (n = 82, r = 0.387, p < 0.001) is greatly inferior to that obtained between C-0 and C-2 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. Copyright (C) 2000 The Canadian Society of Clinical Chemists.