Comparison of predose vs 2-h postdose blood metabolites/cyclosporine ratios in kidney and liver transplant patients.
OBJECTIVE
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 MR(0) values (mean 2.87 +/- 0.12, median 2.48) and MR(2) 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 MR(2) values are significantly lower than the corresponding MR(0), 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.
Fernández-Marmiesse
A
A
Laboratorio Central, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.
Hermida
J
J
Tutor
J C
JC
D001711:Biotransformation; D016572:Cyclosporine / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D016903:Drug Monitoring / Q000379:methods / Q000592:standards; D004655:Emulsions; D006801:Humans; D007118:Immunoassay / Q000379:methods; D016030:Kidney Transplantation / Q000379:methods*; D016031:Liver Transplantation / Q000379:methods*; D018709:Statistics, Nonparametric; D013997:Time Factors
D004655:Emulsions; D016572:Cyclosporine