title: Cyclosporine A and tacrolimus combined with enteric-coated mycophenolate sodium influence the plasma mycophenolic acid concentration - a randomised controlled trial in Chinese live related donor kidney transplant recipients.
abstract: OBJECTIVE
  To observe the different concentrations of mycophenolic acid (MPA) during the early post-transplant phase for various combinations of cyclosporine A (CsA) and tacrolimus (Tac) with enteric-coated mycophenolate sodium (EC-MPS).
  
  
  METHODS
  A total of 42 Chinese adults receiving live related donor kidney transplants were studied. All received a triple immunosuppressive regimen of EC-MPS, CsA/Tac and corticosteroids and were divided randomly into CsA (n = 21) and Tac (n = 21) combination groups. The dosage of EC-MPS was the same (1440 mg/day) in the two groups. The MPA concentration was evaluated with an enzyme-multiplied immunoassay technique (EMIT) and the pharmacokinetic characteristics were investigated in both groups.
  
  
  RESULTS
  The mean maximum plasma concentrations (Cmax ) of MPA in the CsA and Tac groups were 11.365 ± 9.522 and 9.748 ± 7.523 μg/ml, respectively (p = 0.137). The maximum times to Cmax (Tmax ) were 2.54 ± 1.53 and 2.67 ± 1.08 h, respectively (p = 0.341). The mean MPA 12-h areas under the curve (MPA-AUC0-12 h ) were 59.463 ± 16.252 and 77.535 ± 33.615 μg h/ml (p = 0.003) and the mean residence times (MRT) were 3.71 ± 0.829 and 3.928 ± 0.923 h (p = 0.038).
  
  
  CONCLUSIONS
  Combined with the same EC-MPS dosage (1440 mg/day), the MPA-AUC0-12 of the Tac group was higher than that of the CsA group, and the Tac group had a longer MRT after kidney transplantation. Our data indicate that the concentration of MPA should be monitored in clinical therapy when EC-MPS is combined with different calcineurin inhibitors to reduce acute allograft rejection and avoid adverse events.
authors.affiliation: Center of Kidney Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China.
authors.forename: H F
authors.initials: HF
authors.lastname: Huang
authors.forename: X
authors.initials: X
authors.lastname: Yao
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: W Q
authors.initials: WQ
authors.lastname: Xie
authors.forename: J Z
authors.initials: JZ
authors.lastname: Shen-Tu
authors.forename: J H
authors.initials: JH
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002681:China; D016572:Cyclosporine / Q000008:administration & dosage*; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D016030:Kidney Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011446:Prospective Studies; D013608:Tablets, Enteric-Coated; D016559:Tacrolimus / Q000008:administration & dosage*; D066027:Transplant Recipients; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus