Utility of pretransplantation cyclosporine pharmacokinetic studies

Pretransplant cyclosporine (CsA) pharmacokinetic analysis of an individual patient is advocated as a more accurate method of determining the optimal dose schedule of CsA for immediate posttransplant patients than traditional mg/kg dosing methods. Eight adult renal transplant candidates (age range 28-69 years) were studied. CsA whole blood analysis was done with a monoclonal fluorescence polarization immunoassay (mFPIA) and high-performance liquid chromatography HPLC. Noncompartmental modeling methods were used to derive CsA pharmacokinetic values. At 1 and 3 months posttransplant CsA pharmacokinetic analyses were completed on five subjects and the average steady state CsA concentration for the dosing interval, Cav, was compared to predicted values calculated from pretransplant pharmacokinetic parameters for each subject. At 6 months posttransplant, actual and predicted Cav were compared in three subjects. Correlation between predicted and actual Cav at 1 month posttransplant was poor (mean actual Cav = 365 ng/ml versus mean predicted Cav = 238 ng/ml; r2 = 0.361). At 3 months posttransplant, the discrepancy between predicted and actual Cav was greater for all five subjects (r2 = 0.039) and this trend persisted for three subjects at 6 months posttransplantation. The mFPIA analysis overestimated the parent CsA concentration when compared to HPLC analysis; the degree of overestimation ranged from 118 to 180%. The mFPIA assay variability may have contributed to the poor correlation between pre- and posttransplant Cav values. There appears to be little or no basis for subjecting transplant candidates to sophisticated pharmacokinetic tests in order to develop specific CsA dosing guidelines for the posttransplant phase.