MPA Pharmacokinetics in Renal Transplantation

Adequate exposure to mycophenolic acid (MPA) is associated with better outcomes in kidney transplantation. This study evaluated repeated, MPA pharmacokinetics (MPA-PK) according to post-transplant time-points and concomitant CNIs. Fifty-two patients, 33 allocated to tacrolimus (TCL) and 19 to CyA (all with mycophenolate mofetil (MMF) and steroids), had the full MPA area under the time-concentration curve (AUC0-12hrs) repeatedly evaluated at days 7, 14, 30, 60 and 180 post-transplant. MMF daily dose was lower in TCL group as per protocol. Dose-adjusted MPA-AUC0-12hrs progressively increased throughout the study period in both groups but profiles were different according to the CNI regimen and time. The majority of patients were underexposed to MPA on day 7 for both groups what reinforces the need of a higher dose in the first week. Dose-adjusted MPA-AUC0-12hrs was higher in TCL group, after day 7, due to both a diminished MPA clearance (for both groups) and higher AUC4-12hrs in the TCL group. There was a progressive overexposure to MPA in order that at day 180, 21-30% of the patients were overexposed to MPA what indicates a time for MPA monitoring and dose correction for long-term follow-up. These PK data suggest that changes in MPA profile occur according to time and CNIs used and suggests that MPA monitoring may be mandatory at specific time-points.