Lack of correlation between MMF dose and MPA level in pediatric and young adult cardiac transplant patients: does the MPA level matter?
To determine the correlation between mycophenolate mofetil (MMF) dose and mycophenolic acid (MPA) level as well as its impact on rejection among young cardiac transplant recipients (OHT), trough concentrations of MPA and its metabolite, mycophenolic acid glucuronide (MPAG), were measured following MMF doses of 1200 mg/m2/d (max 3000 mg/d). Corresponding endomyocardial biopsy (EMB) grades and calcineurin inhibitor levels were recorded with simultaneous MPA/MPAG levels. Correlation coefficients were derived between MMF dose and MPA/MPAG levels. Contingency analysis evaluated the relation between MPA level and EMB score. Twenty-six patients (median age 15.4 years) had 120 MPA/MPAG levels measured. Average MMF dose was 1208.8 mg/m2/d with median MPA and MPAG concentrations: 2.1 (therapeutic: 1.0-3.5 microg/mL) and 48 microg/mL (reference range: 35-100 microg/mL), respectively. Only 50% of patients consistently achieved therapeutic levels with standard dosing. No correlation was found between MMF dose and MPA/MPAG levels. In the presence of therapeutic calcineurin inhibition, EMB grade > or = 2 occurred more with MPA concentrations < 2.5 microg/mL (p = 0.01). In young OHT patients, MMF dose does not correlate with MPA/MPAG levels, and standard MMF dosing fails to consistently achieve 'therapeutic' MPA concentrations. An MPA trough level < 2.5 microg/mL was more frequently associated with EMB grade > or = 2. Concentration rather than dose-driven management is a more prudent strategy when using MMF.
University of Michigan, C.S. Mott Children's Hospital, Department of Pediatrics, Division of Pediatric Cardiology, Ann Arbor, MI, USA. rjgaj@umich.edu
Robert J
RJ
Gajarski
Dennis C
DC
Crowley
Mary C
MC
Zamberlan
Kathleen D
KD
Lake
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D006084:Graft Rejection / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D007223:Infant; D008499:Medical Records; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012189:Retrospective Studies
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid