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, 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). CONCLUSION: These results suggest that systemic exposures to MPA and its metabolites are not associated with the incidence of diarrhea in liver transplant recipients.
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, 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). CONCLUSION: These results suggest that systemic exposures to MPA and its metabolites are not associated with the incidence of diarrhea in liver transplant recipients.
Authors: M Shipkova; C P Strassburg; F Braun; F Streit; H J Gröne; V W Armstrong; R H Tukey; M Oellerich; E Wieland Journal: Br J Pharmacol Date: 2001-03 Impact factor: 8.739
Authors: T Heller; T van Gelder; K Budde; J W de Fijter; D Kuypers; W Arns; J Schmidt; L Rostaing; S H Powis; K Claesson; I A M Macphee; E Pohanka; J Engelmayer; G Brandhorst; M Oellerich; V W Armstrong Journal: Am J Transplant Date: 2007-05-26 Impact factor: 8.086
Authors: Jose Maria Moreno Planas; Valentin Cuervas-Mons Martinez; Eduardo Rubio Gonzalez; Amparo Gomez Cruz; Javier Lopez-Monclus; Victor Sánchez-Turrion; Jose Luis Lucena Poza; Manuel Jimenez Garrido; Isabel Millan Journal: Am J Transplant Date: 2004-10 Impact factor: 8.086