Pharmacokinetics help optimizing mycophenolate mofetil dosing in kidney transplant patients

Dario Cattaneo, Flavio Gaspari, Silvia Ferrari, Nadia Stucchi, Laura Del Priore, Norberto Perico, Eliana Gotti, Giuseppe Remuzzi

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is now routinely used as immunosuppressant in solid organ transplantation in a fixed daily dose regimen (2 g/d) in association with cyclosporine (CsA) and steroids. However, no correlation has been shown between fixed MMF dose and clinical outcome. Methods: Here we examined the possibility of optimizing MMF dosing by drug pharmacokinetic monitoring in 46 stable kidney transplant recipients. MPA plasma concentration profiles were measured by a reverse-phase high-performance liquid chromatography method 6-9 months after transplantation and related with routine laboratory analysis tests. Since MPA is extensively bound to serum albumin and only the free fraction is pharmacologically active, in a subgroup of 23 patients free plasma MPA was also determined. Results: Despite a comparable MMF dose, a large interindividual variability in both MPA area under the curve (AUC) from 0 to 12 h (range 10.1-99.8 μg/mL·h) and in trough levels (range 0.24-7.04 μg/mL) was found. Patients with AUC > 40 μg/mL·h showed a better (p <0.05) renal function than patients with lower AUC (creatinine clearance 85.7 ± 23.2 versus 64.5 ± 17.5 mL/min), despite no difference in CsA dose, CsA AUC and blood CsA trough level. The percentage of free plasma MPA but not total MPA correlated with the red blood cell and leukocyte count. Conclusions: Therapeutic MMF drug monitoring might contribute to a better management of kidney transplant recipient with the goal of optimizing drug dosing and limiting the risk of MMF-related toxicity.

Original languageEnglish
Pages (from-to)402-409
Number of pages8
JournalClinical Transplantation
Volume15
Issue number6
DOIs
Publication statusPublished - 2001

Keywords

  • Adverse events
  • Anemia
  • Area under the time-concentration curve
  • Free fraction
  • Leukopenia
  • Plasma trough level
  • Renal function

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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