Received July 12, 2007
Accepted on August 6, 2007

ORIGINAL ARTICLES

Pharmacokinetics of Mycophenolate Sodium and Comparison with the Mofetil Formulation in Stable Kidney Transplant Recipients

Dario Cattaneo ^*1, Monica Cortinovis ^*, Sara Baldelli ^*, Alessandra Bitto ^*, Eliana Gotti ^*, Giuseppe Remuzzi ^*, and Norberto Perico ^*

*Department of Medicine and Transplantation, Ospedali Riuniti di Bergamo, Mario Negri Institute for Pharmacological Research, Bergamo, and Center for Research on Organ Transplantation, "Chiara Cucchi De Alessandri & Gilberto Crespi," Bergamo, Italy

¹ To whom correspondence should be addressed. E-mail: dcattaneo{at}marionegri.it.

	Abstract

Background and objectives: The introduction of mycophenolate mofetil has improved graft survival after organ transplantation; however, its use may be limited by important adverse effects. For overcoming these problems, an enteric-coated formulation of mycophenolate sodium has been developed, but pharmacokinetic data of mycophenolic acid release from this formulation are scanty.

Design, setting, participants, & measurements: Pharmacokinetic studies in 32 kidney transplant recipients who were given the enteric-coated formulation of mycophenolate sodium (n = 12) or mycophenolate mofetil (n = 20) were performed. The profiles of mycophenolic acid from the two formulations at months 6, 12, 18, and 24 after transplantation were compared. Subsequently, all patients who were receiving the enteric-coated formulation were shifted to mycophenolate mofetil, and the pharmacokinetic evaluations were repeated.

Results: At month 6 after surgery, aberrant and variable pharmacokinetic curves were found in patients who were given the enteric-coated formulation, whereas those who were taking mycophenolate mofetil had regular mycophenolic acid kinetic profiles. Patients who were taking the enteric-coated formulation had mycophenolic acid time of occurrence for maximum drug concentration that ranged from 0 to 480 min and higher dosage-adjusted mycophenolic acid trough levels compared with patients who were given mycophenolate mofetil. Conversion from the enteric-coated formulation of mycophenolate sodium to mycophenolate mofetil resulted in an improvement of the mycophenolic acid kinetics profiles.

Conclusions: Given the emerging clinical benefit of mycophenolic acid monitoring in the transplant setting, therapeutic drug monitoring problems with the enteric-coated formulation of mycophenolate sodium should be taken into account.