Therapeutic drug monitoring of mycophenolic acid can be used as predictor of clinical events for kidney transplant recipients treated with mycophenolate mofetil

Transplant Proc. 2006 Sep;38(7):2048-50. doi: 10.1016/j.transproceed.2006.06.028.

Abstract

Objective: This study was designed to investigate the relationship between clinical events and the pharmacokinetics of mycophenolic acid (MPA) in adult renal transplant patients.

Methods: Thirty-seven adult kidney transplant recipients received a cyclosporine, mycophenolate mofetil, and steroids. MPA-AUC(0-12) was obtained before and 12 days after grafting by RP-HPLC. Predose blood samples were measured for MPA-C(0) were gathered from all the recipients at 4, 12, and 21 days as well as 1, 1.5, 2, 2.5, 3, and 6 months after grafting. The clinical events at corresponding time points were recorded to correlate with each MPA-C(0) value.

Results: In addition to single-dose and multidose MPA-AUC(0-12), 357 MPA-C(0) values were obtained from 37 patients. The 357 units were divided into three subgroups: group A patients, including 239 units (66.9%), experienced uneventful outcomes; group B of 100 units (28.0%) showed MPA-related side effects, and group C, 18 units (5.0%) of acute rejection episodes. MPA-C(0) for groups A, B, and C were 0.8416 +/- 0.1373 mg/L, 1.5903 +/- 0.3741 mg/L and 0.6057 +/- 0.2338 mg/L, respectively (P < .001 between groups A and B, groups B and C, and P = .021 between groups A and C). The three groups were also divided into an initial phase (< or =1 month, 251 units) and a stable phase (>1 month, 106 units). The relationship between MPA-C(0) and associated clinical events was also investigated.

Conclusion: Our results suggested a relationship between MPA pharmacokinetics and clinical events. The MPA-C(0) might be an appropriate pharmacokinetic monitoring parameter for kidney transplantation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cadaver
  • Drug Monitoring / methods*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation / immunology
  • Kidney Transplantation / physiology*
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / blood
  • Mycophenolic Acid / pharmacokinetics*
  • Mycophenolic Acid / therapeutic use
  • Mycophenolic Acid / toxicity
  • ROC Curve
  • Tissue Donors

Substances

  • Immunosuppressive Agents
  • Mycophenolic Acid