Estimation of Mycophenolic Acid Area Under the Curve With Limited-Sampling Strategy in Chinese Renal Transplant Recipients Receiving Enteric-Coated Mycophenolate Sodium

Jia, Yichen; Peng, Bo; Li, Long; Wang, Jina; Wang, Xuanchuan; Qi, Guisheng; Ren, Ruizhi; Wang, Liming; Qiu, Jianxin; Xu, Ming; Zhu, Tongyu

doi:10.1097/ftd.0000000000000360

Cited by 19 publications

(12 citation statements)

References 30 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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The mycophenolate mofetil (MMF) dose management for optimization of post-transplant treatment especially the early postoperative phase has been well recognized. MMF is a pro-drug of mycophenolic acid (MPA) and is widely used in Chinese renal transplant patients. Until now, the pharmacokinetic (PK) characteristics and model for the area under the concentration–time curve for the 12-h (h) of exposure (AUC0-12 h) of MPA (MPA-AUC0-12 h) estimation were lacking for the new formulation of MMF dispersible tablet in renal transplant patients. The aims of the study were to investigate the PK characteristics of MMF dispersible tablet by detecting the active metabolite of MPA and to establish an accuracy and precision equation for calculating MPA-AUC0-12 h by limited sampling strategy (LSS) in Chinese kidney transplant patients. A total of 60 postoperative kidney transplant recipients were given a multiple-dose of MMF dispersible tablet twice daily combination with tacrolimus (Tac) and steroids. On the 5th day post-transplantation, blood specimens were collected before drug administration and up to 12 h after MMF dispersible tablet administration. Non-compartmental PK analysis was used to determine the data obtained from individual patients. Multivariate stepwise regression analysis was used to develop models for predicting MPA-AUC0-12 h. The 3- and 4-point sampling models using 2 h, 4 h, 8 h and 1 h, 2 h, 4 h and 8 h, respectively, allowed accurate estimation of MPA-AUC0-12 h. PK parameters of MMF dispersible tablet were obtained and the 4-point LSS is the best model for accurate and precise estimation of MPA-AUC0-12 h.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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“…To accurately calculate it, at least 10 blood samples much be collected over 12 hours; thus, this method is costly and difficult to adopt, especially in outpatient departments. As such, limited sampling strategies and pharmacokinetic models have emerged that are simpler to use to estimate the MPA AUC in such settings [ 26 - 28 ].…”

Section: Discussionmentioning

confidence: 99%

The impact of omeprazole on mycophenolate pharmacokinetics in kidney transplant recipients

Abdel-Halim

Kenawy

Demellawy

et al. 2020

Kidney Res Clin Pract

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Background: The absorption rates of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) may be influenced by the concomitant use of omeprazole. Methods: One hundred kidney transplant patients were recruited during their outpatient visits, including 50 on MMF and 50 on EC-MPS. At the clinic, a predose mycophenolic acid (MPA) sample (C 0) was collected; subsequently, the participants received the proton-pump inhibitor omeprazole along with either MMF or EC-MPS. Two more blood samples were collected at 1.5 and 3.5 hours and used to estimate an area under the curve (AUC) from zero to 12 hours [AUC (0-12)]. Results: The mean number of months after transplant was 92 months. The median AUC (0-12) and C 0 results were 62.2 mg•h/L and 2.0 mg/L for the MMF group and 71.9 mg•h/L and 1.8 mg/L for the EC-MPS group (P = 0.160 and 0.225, respectively). Interestingly, 54% of the MMF group and 62% of the EC-MPS group showed AUCs above the target values. The correlation between MPA C 0 and the predicted AUC was poor in both groups. Conclusion: Omeprazole can be safely co-administered with either MMF or EC-MPS, as it did not compromise the MPA exposure. Unexpectedly, however, a high percentage of patients presented MPA AUCs exceeding the target value, highlighting the importance of periodically assessing MPA level.

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“…According to the previous report (12)(13)(14), the patients were randomly assigned to two groups at a 1: 1 ratio: the model group (n = 23) and the validation group (n = 22). An AUC0-12 prediction formula was derived using multiple regression analysis with the model group AUC0-12 as a dependent variable and the plasma concentration at each blood sampling time as an explanatory variable.…”

Section: Discussionmentioning

confidence: 99%

Limited Sampling Strategy for the Estimation of Mycophenolic Acid and its Acyl Glucuronide Metabolite Area under the Concentration-Time Curve in Japanese Lung Transplant Recipients

et al. 2019

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Purpose: The dose of mycophenolate mofetil (MMF) used to prevent rejection after lung transplantation is often adjusted based on the 12-hour area under the concentration-time curve (AUC0-12) of mycophenolic acid (MPA). A limited sampling strategy (LSS) is useful to define the pharmacokinetic (PK) profiles of MPA and mycophenolic acid acyl glucuronide (AcMPAG). Therefore, this study aimed to design a LSS based on multiple linear regression for estimating the AUC0-12 of MPA and AcMPAG at the minimum blood sampling points in Japanese lung transplant patients with concomitant tacrolimus. Methods: Forty-five lung transplantation recipients were enrolled in a PK study of MPA, mycophenolic acid glucuronide (MPAG), and AcMPAG. The plasma MPA, MPAG, and AcMPAG concentrations were determined just before and at 0.5, 1, 2, 4, 8, and 12 hours after dosing. The AUC0-12 of MPA and AcMPAG was calculated using a linear trapezoidal rule from the plasma concentration of each blood sampling time. LSS was used to develop models for estimated AUC in the model group (n = 23) and was evaluated in the validation group (n = 22). Results: The best three time-point equation was 4.04 + 1.64·C1 + 3.08·C4 + 5.17·C8 for MPA, and -0.13 + 3.01·C1 + 3.51·C4 + 5.74·C8 for AcMPAG. The prediction errors (PE) and the absolute prediction errors (APE) were within the clinically acceptable ± 5% and 15% range, respectively (MPA: PE = 2.00%, APE = 11.66%, AcMPAG: PE = 0.98%, APE = 14.69%). The percentage of estimated AUC0-12 within ± 15% of the observed AUC0-12 was 77.27% for MPA and 81.82% for AcMPAG. Conclusion: LSS using three time-point (C1, C4, and C8) provides the most reliable and accurate simultaneous estimation of the AUC0-12 of MPA and AcMPAG in Japanese lung transplant patients.

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Estimation of Mycophenolic Acid Area Under the Curve With Limited-Sampling Strategy in Chinese Renal Transplant Recipients Receiving Enteric-Coated Mycophenolate Sodium

Cited by 19 publications

References 30 publications

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

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

The impact of omeprazole on mycophenolate pharmacokinetics in kidney transplant recipients

Limited Sampling Strategy for the Estimation of Mycophenolic Acid and its Acyl Glucuronide Metabolite Area under the Concentration-Time Curve in Japanese Lung Transplant Recipients

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