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The occurrence of diarrhea not related to the pharmacokinetics of MPA and its metabolites in liver transplant patients

  • Pharmacodynamics
  • Published:
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Abstract

Purpose

Mycophenolate mofetil (MMF) is a pro-drug that is hydrolyzed to release mycophenolic acid (MPA). Subsequently MPA is extensively metabolized to phenyl mycophenolic acid glucuronide (MPAG) and MPA acyl glucuronide (AcMPAG). It was presumed that the closest association is between plasma AcMPAG concentrations and the incidence of diarrhea. This study aimed to investigate the correlation between pharmacokinetics of MPA, MPAG, and AcMPAG and diarrhea in liver transplant recipients on MMF with tacrolimus.

Methods

Sixty-seven patients receiving liver transplantation were included. The pharmacokinetics of MPA and its metabolites were monitored repeatedly in the early stage (within 2 weeks) and in the late stage after transplant. The plasma concentrations of MPA, MPAG, and AcMPAG were determined by the HPLC method.

Results

Twenty-two patients (32.8%) suffered from episodes of diarrhea. Compared with the data from the early stage, AUC0–12h of MPA, MPAG, and AcMPAG increased significantly in both groups in the later stage. AUC0-12h of MPA, MPAG, and AcMPAG were not different significantly between the group with diarrhea and the group without diarrhea, either in the early stage or in the late stage (P > 0.05).

Conclusion

These results suggest that systemic exposures to MPA and its metabolites are not associated with the incidence of diarrhea in liver transplant recipients.

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Acknowledgements

This study was supported by Natural Science Foundation of Shanghai (no. 08ZR1414200). The authors have no conflicts of interest that are directly relevant to the content of this study. The authors would like to thank Dr. Lu Hui for his help in revising the manuscript and all nurses of the Center for Organ Transplantation.

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Authors and Affiliations

  1. Institute of Clinical Pharmacology, Ruijin Hospital, Shanghai Jiaoton University School of Medicine, Shanghai, People’s Republic of China

    Zhang Wei Xia & Chen Bing

  2. Center for Organ Transplantation, Ruijin Hospital, Shanghai Jiaoton University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, People’s Republic of China

    Chen Yong Jun, Chen Hao, Shi Min Min & Xie Jun Jie

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  1. Zhang Wei Xia
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  2. Chen Yong Jun
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  3. Chen Hao
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  4. Chen Bing
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Correspondence to Chen Hao.

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Zhang Wei Xia and Chen Yong Jun contributed equally to this article and can be considered to be co-first authors.

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Xia, Z.W., Jun, C.Y., Hao, C. et al. The occurrence of diarrhea not related to the pharmacokinetics of MPA and its metabolites in liver transplant patients. Eur J Clin Pharmacol 66, 671–679 (2010). https://doi.org/10.1007/s00228-010-0833-2

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  • DOI: https://doi.org/10.1007/s00228-010-0833-2

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