A limited sampling strategy for the estimation of 12-hour cyclosporine neoral area under the curve in Chinese cardiac transplant recipients

Abstract

Introduction: This study determined the accuracy of a limited sampling strategy to predict the 12-hour cyclosporine neoral (CsA) area-under-the-curve (AUC) to provide a practical method for more accurate therapeutic drug monitoring (TDM) of CsA in Chinese heart transplant recipients.

Methods: 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 CsA oral administration in 13 de novo heart recipients receiving oral CsA bid after rabbit antithymoglobulin sequential immuno-induction. Pharmacokinetics were analyzed for the first dose (PK-1) and the steady state dose (PK-2, 1 month after transplantation). The limited sampling strategies included single-point, 2-point, and 3-point prediction of AUC using multiple linear regression analyses.

Results: Comparing the AUC/mg dose, PK-1 was much lower than PK-2 (25.2 +/- 11.4 ng x h/mg x mL vs 45.4 +/- 12.9 ng x h/mg x mL; P = .0005 using paired t test). The correlations of each single-point blood level of PK-1 with the AUC were lower than those of the corresponding sampling time in PK-2. In the PK-2 study, C4 had the best correlation (r2 = 0.732; P = .00) as a single-point to predict AUC, but the 2-point C2 + C12 had a higher correlation (r2 = 0.937; P = .00). Among the 3-point combinations, C2 + C4 + C12 showen the best prediction (r2 = 0.982; P = .00) of the AUC in PK-2.

Conclusion: The bioavailability of CsA was lower in PK-1 than in PK-2. At steady state, we recommend C2 + C12 to predict AUC because it is accurate and not labor-intensive.