The occurrence of diarrhea not related to the pharmacokinetics of MPA and its metabolites in liver transplant patients.
OBJECTIVE
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, AUC(0-12h) of MPA, MPAG, and AcMPAG increased significantly in both groups in the later stage. AUC(0-12h) 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).


CONCLUSIONS
These results suggest that systemic exposures to MPA and its metabolites are not associated with the incidence of diarrhea in liver transplant recipients.
Xia
Zhang Wei
ZW
Institute of Clinical Pharmacology, Ruijin Hospital, Shanghai Jiaoton University School of Medicine, Shanghai, People's Republic of China.
Jun
Chen Yong
CY
Hao
Chen
C
Bing
Chen
C
Min
Shi Min
SM
Jie
Xie Jun
XJ
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003967:Diarrhea / Q000139:chemically induced*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016559:Tacrolimus / Q000008:administration & dosage
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus
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