Usefulness of limited sampling strategy for mycophenolic acid area under the curve considering postoperative days in living-donor renal transplant recipients with concomitant prolonged-release tacrolimus

BACKGROUND: The optimal dose of mycophenolate mofetil (MMF) in renal transplant patients has been recommended to be decided on the basis of area under the concentration-time curve (AUC(0-12)) of mycophenolic acid (MPA). Although meta-analysis has revealed that postoperative day (POD) is an influencing factor in MPA pharmacokinetics, there are no reports regarding a limited sampling strategy (LSS) for MPA AUC in consideration of POD. The aim of this study was to construct of an LSS considering POD that appropriately expresses the MPA AUC following renal transplantation and evaluation of the usefulness. METHODS: Serum concentration–time profiles (measured AUC(0-12)) comprising nine sampling points over 12 h were analyzed in 36 living-donor renal transplant recipients after MMF administration with concomitant once-daily prolonged-release tacrolimus. Two LSSs were developed by stepwise multiple regression analysis (Method A: not classified by PODs; Method B: classified by PODs into POD < 31 and POD ≥ 31). Each LSS comprised four blood-sampling points within 6 h after MMF administration. Precision and reliability were verified by using root-mean-square error (RMSE), correlation coefficient (R(2)), and coefficient of determination (q(2)) by using leave-one-out cross-validation. The absolute values of the difference between measured and estimated AUCs (delta AUC) were compared for both estimating equations. RESULTS: One-hundred samples obtained from 36 recipients for AUC(0-12) comprised POD < 31 (n = 39) and POD ≥ 31 (n = 61). Estimation of AUC(0-12) by Method B resulted in better accuracy and reliability (Method A: RMSE = 5.5, R(2) = 0.85, q(2) = 0.83; Method B: POD < 31: RMSE = 5.5, R(2) = 0.86, q(2) = 0.83; POD ≥ 31: RMSE = 3.9, R(2) = 0.92, q(2) = 0.89) and significantly lower median delta AUC compared with that by Method A (delta AUC: 2.6 (0.0–11.6) v.s. 3.9 (0.1–18.1), p = 0.032). CONCLUSION: These results suggest that LSS, classified as POD < 31 or POD > 31, would provide more accurate and reliable estimation of MPA AUC(0-12) in Japanese living-donor renal transplant patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40780-017-0086-7) contains supplementary material, which is available to authorized users.