K. Yamaguchi, M. Watanabe, T. Motoki, H. Tanaka, M. Asakura, T. Tai, K. Takahashi, T. Nozaki, S. Kosaka, H. Houchi; Department of Pharmacy, Kagawa University Hospital, Miki-cho, Kita-gun, Japan

BACKGROUND: Mycophenolate mofetil 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 (AUC0-12h) of MPA is considered to be an effective pharmacokinetics parameter for predicting acute rejection. However, frequent blood sampling is required to calculate AUC0-12h, which imposes a burden on patients and providers. Therefore, we examined a limited sampling strategy for estimation of MPA-AUC0-12h in Japanese living-related renal transplant recipients.
METHODS: Among the patients who received renal transplantation at Kagawa University Hospital, the subjects of this study were 22 patients for whom we could calculate MPA-AUC0-12h by the linear trapezoidal rule. The observation period was from February 2011 through April 2012. Blood samples were collected immediately before administration and at 1, 2, 4, 6, 8 and 12 h (C0,C1,...,C12) after administration. We carried out single and multiple regression analysis with MPA-AUC0-12h as a dependent variable.
RESULTS: AUC0-12h was positively correlated with C0 and all simple AUCs, and the relationship was stronger in the order of AUC0-4h (R2 = 0.64) > AUC0-2h (R2 = 0.59) > AUC0-1h (R2 = 0.54) > C0 (R2 = 0.25). On the other hand, a model based on C0 and C4 provided the highest estimation of MPA-AUC0-12h for pre-Transplantation (Tx) (R2 = 0.91) and 1 month post-Tx (R2 = 0.48). Furthermore, a model based on C0 and C6 provided the highest estimation of MPA-AUC0-12h for 3 months post-Tx (R2 = 0.60).
CONCLUSION: The present study provides useful information for effective and efficient monitoring of MPA levels in Japanese living-related renal transplant recipients.