Relationship Between Acute Rejection and Cyclosporine or Mycophenolic Acid Levels in Japanese Heart Transplantation

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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 30s; woman in her 40s) had acute rejection with a mycophenolic acid(MPA) AUC_<0-12h> <30μg・h・ml^<-1> and low CsA AUC(AUC_<0-4h>; 2,408 ng・h・ml^<-1>, 1,735ng・h・ml^<-1>). However, 1 patient(man in his 30s) with a high CsA AUC_<0-4h>(4,019ng・h・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 C_0, C_2, AUC_<0-4h> and MPA AUC_<0-12h>. Conclusions The findings suggest that a high CsA AUC_<0-4h> may prevent rejection of a cardiac allograft, even if MMF is stopped or drastically reduced.
社団法人日本循環器学会の論文
2007-02-20