title: The occurrence of diarrhea not related to the pharmacokinetics of MPA and its metabolites in liver transplant patients.
abstract: 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.
authors.affiliation: Institute of Clinical Pharmacology, Ruijin Hospital, Shanghai Jiaoton University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Zhang Wei
authors.initials: ZW
authors.lastname: Xia
authors.forename: Chen Yong
authors.initials: CY
authors.lastname: Jun
authors.forename: Chen
authors.initials: C
authors.lastname: Hao
authors.forename: Chen
authors.initials: C
authors.lastname: Bing
authors.forename: Shi Min
authors.initials: SM
authors.lastname: Min
authors.forename: Xie Jun
authors.initials: XJ
authors.lastname: Jie
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus
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