Takada M, Wada K,Ueda T, Ochi H, Kotake T, Morishita H, Hanatani
A, Nakatani T.
Relationship between acute
rejection and cyclosporine or mycophenolic acid levels in
Japanese heart transplantation.
Circ J. 2007 Mar;71(3):289-93.
Division of Practical Pharmacy, Faculty of Pharmaceutical
Sciences, Kinki University, Osakayama, Japan.
kwada@hsp.ncvc.go.jp
BACKGROUND: Cyclosporine (CsA), Mycophenolate mofetil (MMF) and
prednisolone (PSL) are widely used for the prevention of acute
rejection after heart transplantation. Recently, the serum
concentration - time curves (AUC) of CsA and MMF have been
demonstrated to be precise predictors of acute rejection.
METHODS AND RESULTS: Fourteen heart transplant patients were
treated concomitantly with CsA, MMF, and PSL between May 1999
and November 2005 at the National Cardiovascular Center and of
them 3 had acute rejection episodes [International Society for
Heart & Lung Transplantation grade 3a]. Two patients (man in his
30 s; woman in her 40 s) had acute rejection with a mycophenolic
acid (MPA) AUC(0-12 h) <30 microg x h x ml(-1) and low CsA AUC
(AUC(0-4 h); 2,408 ng x h x ml-1, 1,735 ng x h x ml-1). However,
1 patient (man in his 30 s) with a high CsA AUC(0-4 h) (4,019 ng
x h x ml-1) did not develop cardiac allograft rejection even if
the MMF was temporarily stopped. These 3 patients were
investigated to evaluate the relationship between acute
rejection and pharmacokinetic parameters, including the CsA C0,
C2, AUC(0-4 h) and MPA AUC(0-12 h). CONCLUSIONS: The findings
suggest that a high CsA AUC(0-4 h) may prevent rejection of a
cardiac allograft, even if MMF is stopped or drastically
reduced.
PMID: 17322623 |
