Comparison of pharmacokinetics of mycophenolic acid and its metabolites between living donor liver transplant recipients and deceased donor liver transplant recipients

Abstract

Living-donor liver transplantation (LDLT) has been considered an alternative method for treatment of patients with end-stage liver disease. However, the characteristics of pharmacokinetics of mycophenolic acid (MPA) in patients who underwent LDLT were not clear. This study was designed to compare the pharmacokinetics of MPA and its metabolites between LDLT patients and deceased donor liver transplant (DDLT) patients after oral administration of mycophenolate mofetil (MMF). Thirteen patients who underwent LDLT and 14 patients who underwent DDLT were enrolled prospectively. All patients received oral MMF administration (1.0 g, twice daily) in combination with tacrolimus (TAC). The plasma concentrations of MPA, free MPA, glucuronide (MPAG), and acyl glucuronide (AcMPAG) was determined by high-performance liquid chromatography method. There was a wide variation in various pharmacokinetic parameters of MPA and its metabolites in patients who underwent LDLT and DDLT after oral MMF administration. Although mean MPA area under the plasma concentration time curve for 0-12 hours (AUC 0-12h ) of MPA and MPAG in DDLT patients were higher than those in LDLT patients, there was no significant difference between the two groups. MPA concentration at 6 hours (C 6h ), C 10h , C 12h , and MPA AUC 6-12h were significantly higher in DDLT group than those in LDLT group (P Ͻ 0.05). Inversely, higher free MPA AUC 0-12h and significant free MPA fraction (P Ͻ 0.05) in LDLT patients were observed in DDLT patients when compared with DDLT group. AcMPAG concentrations at 4, 8, and 10 hours and AcMPAG AUC 0-12h were significantly higher in the DDLT group (P Ͻ 0.05). In conclusion, after a fixed oral dose of MMF, DDLT patients had higher enterohepatic recycling contributing to total MPA exposure compared with LDLT patients. The function of glucuronide conjugation in LDLT patients was decreased compared with that in DDLT patients. Higher free MPA AUC 0-12h and a significantly higher fraction of free MPA in LDLT patients suggested that a lower oral dose of MMF may be administered for patients who underwent LDLT.

Comparison of a Point-of-Care Testing with Enzyme-Multiplied Immunoassay Technique and Liquid Chromatography Combined With Tandem Mass Spectrometry Methods for Therapeutic Drug Monitoring of Mycophenolic Acid: A Preliminary Study

“…TDM is an important tool for personalized immunosuppressive therapy, by which optimal effects can be obtained, minimizing potential toxicities. 10,18,19 Several analytical methods, especially chromatography and immunoassays, are developed and currently available for determining the concentration in routine TDM of MPA. However, the application of these methods is limited at large hospitals or research institutes because of the expensive machine and high requirements for the sites.…”

Pharmacokinetics of mycophenolic acid after haplo-hematopoietic stem cell transplantation in Japanese recipients

“…As a result, AUC 6-12h / AUC 0-12h which was approximately 0.3-0.4 when patients were administered MMF with tacrolimus in solid organ transplantation was calculated to be approximately 0.2 on both days 14 and 28 in this study, suggesting that MPA EHC did not occur in haplo-HSCT recipients. [17][18][19]25 Additionally, it is common for solid organ transplantation recipients to be administered PPIs like HSCT recipients. We speculated that plasma MPA concentration did not increase on day 28 owing to the absence of MPA EHC.…”