Abstract

The purpose of this study was to assess the clinical utility of mycophenolic acid (MPA) trough concentration monitoring in heart transplant recipients.
Methods: We reviewed 456 MPA plasma level measurements (EMIT/Dade-Behring) which were performed in 76 pts. after orthotopic heart transplantation (OHT): 57 M and 21 F, age 41.9±16, time after OHT (months) 17.6±24. Daily dose of mycophenolate mofetil (MMF) was 2-3 g before MPA measurement introduction, then it was adjusted to achieve MPA trough levels (TL) of 2-4 µg/ml. Additionally pts. received either cyclosporine-A (CyA) or tacrolimus and prednisone. We analyzed first MPA levels obtained in pts. without previous monitoring, then we looked for a relation between CyA or tacrolimus and MPA level, and finally we checked for a relation between MPA level and the side-effects of MMF.
Results: In a group of 59 pts. without earlier MPA level monitoring we found that 36 pts. (61%) had MPA level below, 19 pts. (32%) within, and 4 pts. (7%) above target TL. We identified a group of 11 pts. (characterized by unstable CyA TLs and liver impairment) with a significant positive correlation between CyA and MPA level. For the remaining group of pts. we found a non-significant negative correlation between CyA and MPA concentrations. Target MPA TL was achieved in 40% of cases in pts. with CyA TL below 200 ng/ml (Axsym/Abbott), in 40% of cases in pts. with CyA TL 200-300 ng/ml, and in 27% of cases in pts. with CyA TL over 300 ng/ml. There was no correlation between tacrolimus and MPA level. MPA TL over 4 µg/ml occurred in 22% of results from pts. receiving tacrolimus (n=6) and 11% of pts. on CyA (n=17, p=0.011). 90% of these pts. had symptoms of GI irritation, 33% – leucopoenia, and 14% – anemia.
Conclusions: It is uncommon to achieve MPA TL of 2-4 µg/ml with typical doses of MMF, especially with concomitant high CyA TL. Typical side effects of MMF should be an indication to check MPA TL.

Keywords: Heart Transplantation, Mycophenolate Mofetil, Mycophenolic Acid Trough Concentration Measurement