Mycophenolate pharmacokinetics and inosine monophosphate dehydrogenase activity in liver transplant recipients with an emphasis on therapeutic drug monitoring

Abstract

Background. The pharmacokinetics of the immunosuppressant mycophenolic acid (MPA) demonstrates high inter- and intra-patient variability. Variation in the binding of MPA to albumin has been postulated to be an important factor in this variability, and monitoring of free MPA has been suggested to improve therapeutic drug monitoring (TDM) of MPA. Inosine monophosphate dehydrogenase (IMPDH) is the target enzyme for MPA, therefore the IMPDH activity in lymphocytes can serve as a marker of the MPA-specific response. This study aimed to explore how the albumin concentration influences the free concentration of MPA in liver transplant recipients and to assess whether alteration in the free MPA influences IMPDH activity in CD4 + cells. Methods. Blood samples were taken from 20 liver transplant recipients on two separate occasions (days 3–5 and 16–21). Total and free concentrations of MPA, and IMPDH activity were measured during the first 4 h of each dose interval. Results. Albumin levels correlated with the free fraction of MPA. However, the total MPA and free MPA were equal predictors of the immunosuppressive response as defined by IMPDH activity. Conclusion. Total and free MPA are equally good predictors of the immunosuppressive effect exerted by MPA as defined by IMPDH activity. IMPDH activity measurements represent a promising approach to TDM in patients treated with MPA.