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 0-12 h ) of MPA is considered to be an effective pharmacokinetics parameter for predicting acute rejection. However, frequent blood sampling is required to calculate AUC 0-12 h , which imposes a burden on patients and providers. Therefore, we examined a limited sampling strategy (LSS) for estimation of MPA-AUC 0-12 h using only a trough level (C 0 ) and two points including C 0 in Japanese living-related renal transplant recipients with concomitant extended-release tacrolimus (ER-TAC). The present study suggests that better estimation of MPA-AUC 0-12 h can be obtained by using two points including C 0 as compared with only C 0 regardless of transplant progress. Furthermore, blood collection points showing the highest estimation of MPA-AUC 0-12 h by adding to C 0 were C 4 at pre-transplantation (Tx) and 1 month post-Tx, and C 6 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.

Pharmacokinetics of Mycophenolate Mofetil and Development of Limited Sampling Strategy in Early Kidney Transplant Recipients

“…Some researches have shown that the trough level of MPA may be correlated to the patient’s outcomes in kidney transplant recipients ( Borrows et al, 2006 ; Miura et al, 2011 ). However, many studies have indicated a poor correlation between single-point concentrations and MPA-AUC 0-12 h ( Barraclough et al, 2012a ; Chaabane et al, 2013 ; Yamaguchi et al, 2013 ; Cai et al, 2015 ; Jia et al, 2017 ). The present study also revealed the same result.…”

“…Then, we used the stepwise analysis obtained the equations were listed in Table 4 . In the past reports, there were also no models which include single sample concentration could accuracy predict the fAUC of MPA in renal transplant recipients ( Pawinski et al, 2002 ; Baraldo et al, 2009 ; Miura et al, 2009 ; Yamaguchi et al, 2013 ; Cai et al, 2015 ). As a result, two time points ( C 2 and C 8 ), three time points ( C 2 , C 4 , and C 8 ) and four time points ( C 1 , C 2, C 4 , and C 8 ) models were developed in this study.…”

Pharmacokinetics and target attainment of mycophenolate in pediatric renal transplant patients

“…In other words, the AUC 0–4h does not reflect the total exposure (AUC 0–12h ) similarly in different phases after renal transplantation. Previous research already showed that different limited sampling strategies are needed depending on the period post‐transplantation . Moreover, when using AUC 0–4h , a very strict adherence to the sampling protocol is required .…”

Associations of UDP-glucuronosyltransferases polymorphisms with mycophenolate mofetil pharmacokinetics in Chinese renal transplant patients

“…Venous blood samples were collected at 0.5, 1.5, 4, and 9 h after the morning dose of MMF. We used a validated abbreviated sampling strategy to estimate the AUC 0-12 h of MPA and MPAG instead of a full time-concentration profile [18,19] . Briefly, blood samples before and 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 9.0, and 12.0 h after the MMF morning dose were obtained from 42 adult renal transplant patients who used a fixed MMF dose combined with tacrolimus for at least 2 weeks.…”