Clinical application of monitoring mycophenolic acid trough concentration in heart transplant recipients--single center's experience.
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 microg/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 microg/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 microg/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.
Zakliczyński
Michał
M
Dept. of Cardiac Surgery & Transplantation, Silesian Center for Heart Disease, Zabrze, Poland. zaklimed@onet.pl
Szewczyk
Marta
M
Zakliczyńska
Helena
H
Zembala
Marian
M
D000328:Adult; D015331:Cohort Studies; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008099:Liver / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood* / Q000627:therapeutic use; D009994:Osmolar Concentration; D011159:Population Surveillance; D011182:Postoperative Care; D011184:Postoperative Period; D012189:Retrospective Studies; D016559:Tacrolimus / Q000097:blood; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus