Relationship between acute rejection and cyclosporine or mycophenolic acid levels in Japanese heart transplantation

Abstract

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) AUC0-12 h <30 μg·h· ml-1 and low CsA AUC (AUC0-4 h; 2,408 ng·h· ml-1, 1,735 ng·h·ml-1). However, 1 patient (man in his 30s) with a high CsA AUC0-4 h (4,019 ng·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 C0, C2, AUC0-4 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.