Therapeutic drug monitoring of tacrolimus in cardiac transplant recipients: A comparison with cyclosporine neoral

Abstract

This study compares the pharmacokinetics of tacrolimus (TAC) and cyclosporine Neoral (CsA) in cardiac transplant recipients. Methods Twenty-six de novo cardiac recipients were prospectively and randomly assigned to receive oral TAC- or CsA-based regimens after 5 to 6 days of rabbit antithymocyte globulin induction. Blood samples were collected at 0 (before the dose) and 0.5, 1, 2, 3, 4, 6, 8, 10, as well as 12 hours after drug administration. The pharmacokinetics of the first dose (PK-1) and at steady state (PK-S, 1 month after transplantation) were analyzed. Results Comparing the AUC per milligram dose, there was no significant difference between PK-1 and PK-S among TAC (46.0 ± 24.3 ng.h/mg.mL versus 69.0 ± 43.9 ng.h/mg.mL, P = .15 by paired t-test), but a significant difference in CsA (25.2 ± 11.4 ng.h/mg.mL versus 45.4 ± 12.9 ng.h/mg.mL, P = .0005 by paired t-test). This means better TAC absorption in the early post–heart transplant period. Using a single-point blood level to predict AUC, TAC showed a significantly higher correlation than CsA at all corresponding sampling times. Besides, C12 in both PK-1 and PK-S of TAC displayed good correlations to the AUC ( r 2 = .895, P = .00 in PK-1 and r 2 = .81, P = .00 in PK-S). The TAC trough level was accurate enough to predict the AUC. Conclusion The pharmacokinetic profile of TAC is more reliable than that of CsA in the early post–heart transplant period. A high correlation of trough blood levels with AUC omits the requirement for a multiple sampling strategy to more accurately measure AUC as is needed with CsA.