A Prospective Study To Investigate Mycophenolic Acid (MPA) Exposure Through Area Under The Curve (AUC) in Renal Transplants Recipients Treated With Mycophenolate Mofetil (MMF) or Enteric Coated Mycophenolate Sodium (EC-MPS).

Introduction: mychophenolic acid (MPA) is the active component of the mofetil mycophenolate and sodium mycophenolate widely applied on immunosuppressive therapyin solid organ transplantation.Pharmacokinetic studies have demonstrated an increased risk of acute rejection in patients under exposure to MPA. This drug has a small therapeutic window, but usually therapeutic monitoring is not performed. Aims: to evaluate the frequency of stable renal transplants recipients taking mycophenolic acid (MMF or EC-MPS) with MPA AUC out of target level (30mcg*h ml-1). Materials and methods: it was planed to selected 100 patients above sixth month post-renal transplantation. We present the partial results of 40 selected patients that performed an MPA AUC by High Performance Liquid Chromatography (HPLC), 9 patients using MMF and 31 patients using MPS.Results: 32% of the patients were out of target level. 15% were above the target (60mcg*h ml-1) and 17% were below the target level. Three out of 9 patients taking MMF had MPA AUC below target level. All 3 patients used proton pump inhibitor. Two were taking MMF full dose (2g/day) associated with CsA. The third was taking 1g/day associated with Tac. One patient presented level above the target was taking 1g/day of MMF associated with TAC without proton pump inhibitor. Nine (29%) out of 31 patients taking MPS were out of the target level. Four (13%) were below and 16% were above the target level. All 4 patients presenting low levels were taking lower dose (three: 720mg/day and one: 360mg/day) associated with Tac. Four patients above the target were taking full dose of EC-MPS (2 with TAC and 2 with CsA) and one 1080g/day with TAC. The patients had the dose adjusted to reach 30 to 60 mg*h ml-1. Conclusion: In this initial assessment, around one third of patients had levels outside the MPA reference value. Half of these patients with decreased level were under MMF associated to proton pump inhibitor or taking MPS at low doses. Therefore, it seems the MPA AUC is important to evaluate kidney transplantation patients to avoid the risk of under or over immunosuppression.