Mycophenolic acid metabolite levels in pediatric liver transplantation: Correlation with a limited sampling strategy

Thomas M. Attard, Anil Dhawan, J. Michael Tredger, Kim Conner, Karen Kling, Paul Colombani, Richard Thompson, Carmen Cuffari

Research output: Contribution to journalArticle

Abstract

Background: Although mycophenolate mofetil (MMF) has proven efficacy in preventing solid organ allograft rejection in adults, well-established dosing practices have yet to be established in children.This has led to the notion of developing therapeutic drug-monitoring techniques based on measuring the active mycophenolic acid (MPA) metabolite. Aim: The aim of this study is to establish an effective measure of plasma MPA metabolite levels based on a limited sampling strategy in pediatric liver transplant recipients. Plasma MPA levels were also correlated with conventional MMF dosing practices and concomitant immunosuppression. Methods: Plasma MPA metabolite levels were measured in 41 (23 female, 18 male) patients post (>7days) liver transplant from 2 major pediatric transplant centers by either a high performance liquid chromatographic or EMIT™ monitoring assay technique.The formal plasma MPA AUC was compared to an estimated MPA AUC by regression analysis. Results: Plasma MPA AUC(0-8 h) metabolite levels correlated well with a limited sampling strategy based on the following equation: 9.1 + 5.7 x C0 + 1.1 x C40 min + 2.1 x C2h (R = 0.74).There was a wide inter-patient variability in plasma MPA AUC metabolite levels despite conventional drug dosing practices. Patients on concomitant cyclosporine required higher mean (SEM) doses (548 [71] mg/day) of MMF compared to patients on tacrolimus (285 [71] mg/day) therapy (P < 0.02). Conclusion: Plasma MPA metabolites can be monitored in children post liver transplantation based on a limited sampling strategy. Future studies are needed to determine whether MMF therapy can be effectively tailored to improve overall clinical response based on the notion of therapeutic MPA metabolite monitoring.

Original languageEnglish (US)
Pages (from-to)135-142
Number of pages8
JournalJournal of Applied Research
Volume8
Issue number2
StatePublished - 2008

Keywords

  • Liver transplantation
  • Metabolites
  • Mycophenolate mofetil
  • Pediatrics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Mycophenolic acid metabolite levels in pediatric liver transplantation: Correlation with a limited sampling strategy'. Together they form a unique fingerprint.

  • Cite this