Therapeutic drug monitoring of tacrolimus in cardiac transplant recipients: a comparison with cyclosporine neoral.
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 x h/mg x mL versus 69.0 +/- 43.9 ng x h/mg x mL, P = .15 by paired t-test), but a significant difference in CsA (25.2 +/- 11.4 ng x h/mg x mL versus 45.4 +/- 12.9 ng x h/mg x 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 (r2 = .895, P = .00 in PK-1 and r2 = .81, P = .00 in PK-S). The TAC trough level was accurate enough to predict the AUC.


CONCLUSIONS
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.
Wang
C H
CH
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Ko
W J
WJ
Chou
N K
NK
Wang
S S
SS
D000961:Antilymphocyte Serum / Q000627:therapeutic use; D019540:Area Under Curve; D001682:Biological Availability; D001835:Body Weight; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D016027:Heart Transplantation / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus