Limited Sampling Strategy for the Estimation of Mycophenolic Acid Area Under the Concentration-Time Curve Treated in Japanese Living-Related Renal Transplant Recipients with Concomitant Extended-Release Tacrolimus

Abstract

Mycophenolate mofetil (MMF) is used for oral administration to prevent rejection in renal transplant recipients, and is rapidly converted into mycophenolic acid (MPA), the active metabolite, by hydrolysis in vivo. The area under the concentration-time curve (AUC_0–12h) of MPA is considered to be an effective pharmacokinetics parameter for predicting acute rejection. However, frequent blood sampling is required to calculate AUC_0–12h, which imposes a burden on patients and providers. Therefore, we examined a limited sampling strategy (LSS) for estimation of MPA-AUC_0–12h using only a trough level (C₀) and two points including C₀ in Japanese living-related renal transplant recipients with concomitant extended-release tacrolimus (ER-TAC). The present study suggests that better estimation of MPA-AUC_0–12h can be obtained by using two points including C₀ as compared with only C₀ regardless of transplant progress. Furthermore, blood collection points showing the highest estimation of MPA-AUC_0–12h by adding to C₀ were C₄ at pre-transplantation (Tx) and 1 month post-Tx, and C₆ at 3 months post-Tx. We conjecture that changes in renal function and serum albumin (Alb) accompanying transplant progress are aggravating factors in terms of estimation, because there was also a significant difference in the reciprocal of serum creatinine (1/Scr) and Alb between pre-Tx and post-Tx in this study. In conclusion, the present study provides useful information for effective and efficient monitoring of MPA levels in Japanese living-related renal transplant recipients.