title: 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.
  
  
  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.
authors.affiliation: Division of Practical Pharmacy, Faculty of Pharmaceutical Sciences, Kinki University, Osakayama, Japan. kwada@hsp.ncvc.go.jp
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Wada
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Takada
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ochi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kotake
authors.forename: Hideki
authors.initials: H
authors.lastname: Morishita
authors.forename: Akihisa
authors.initials: A
authors.lastname: Hanatani
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakatani
mesh_terms: D000328:Adult; D019540:Area Under Curve; D016572:Cyclosporine / Q000009:adverse effects* / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000139:chemically induced*; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007564:Japan; D008297:Male; D009173:Mycophenolic Acid / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D011237:Predictive Value of Tests; D011239:Prednisolone / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D016572:Cyclosporine; D011239:Prednisolone; D009173:Mycophenolic Acid