UTILITY OF PRETRANSPLANTATION CYCLOSPORINE PHARMACOKINETIC STUDIES

Pretransplant cyclosporine (CsA) pharmacokinetic analysis of an indivi dual patient is advocated as a more accurate method of determining the optimal dose schedule of CsA for immediate posttransplant patients th an traditional mg/kg dosing methods. Eight adult renal transplant cand idates (age range 28-69 years) were studied. CsA whole blood analysis was done with a monoclonal fluorescence polarization immunoassay (mFPI A) and high-performance liquid chromatography HPLC. Noncompartmental m odeling methods were used to derive CsA pharmacokinetic values. At 1 a nd 3 months posttransplant CsA pharmacokinetic analyses were completed on five subjects and the average steady state CsA concentration for t he dosing interval, Ca(av), was compared to predicted values calculate d from pretransplant pharmacokinetic parameters for each subject. At 6 months posttransplant, actual and predicted C(av) were compared in th ree subjects. Correlation between predicted and actual C(av) at 1 mont h posttransplant was poor (mean actual C(av) = 365 ng/ml versus mean p redicted C(av) = 238 ng/ml; r2 = 0.361). At 3 months posttransplant, t he discrepancy between predicted and actual C(av) 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 o f overestimation ranged from 118 to 180%. The mFPIA assay variability may have contributed to the poor correlation between pre- and posttran splant C(av) values. There appears to be little or no basis for subjec ting transplant candidates to sophisticated pharmacokinetic tests in o rder to develop specific CsA dosing guidelines for the posttransplant phase.