Therapeutic monitoring of mycophenolate in transplantation: Is it justified?

Barraclough, K.A., Staatz, C.E., Isbel, N.M. and Johnson, D.W. (2009) Therapeutic monitoring of mycophenolate in transplantation: Is it justified?. Current Drug Metabolism, 10 2: 179-187. doi:10.2174/138920009787522205

Author Barraclough, K.A.
Staatz, C.E.
Isbel, N.M.
Johnson, D.W.
Title Therapeutic monitoring of mycophenolate in transplantation: Is it justified?
Journal name Current Drug Metabolism   Check publisher's open access policy
ISSN 1389-2002
Publication date 2009-02-01
Year available 2009
Sub-type Article (original research)
DOI 10.2174/138920009787522205
Open Access Status
Volume 10
Issue 2
Start page 179
End page 187
Total pages 9
Editor Chandra Prakash
Place of publication Hilversum, Netherlands
Publisher Bentham Science Publishers
Language eng
Subject C1
111502 Clinical Pharmacology and Therapeutics
920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified
1103 Clinical Sciences
110312 Nephrology and Urology
Abstract Mycophenolate mofetil (MMF) is the preferred antimetabolite in solid organ transplantation. It is a prodrug that undergoes pre-systemic metabolism to mycophenolic acid (MPA), the active drug moiety. MMF is typically administered as a fixed dose without routine monitoring of MPA concentrations. However, a role for therapeutic drug monitoring (TDM) of MPA has been suggested based on the drug's narrow therapeutic window and considerable between-subject variability. Dose-normalized MPA area under the concentration- time curve (AUC) has been observed to vary ≥10-fold. Some of this variability may be accounted for by patient variability in renal and liver function, serum albumin and haemoglobin levels, body mass, concomitant medication exposure and genetic polymorphisms in enzymes responsible for drug metabolism and transport, but much is unexplained. Widespread adoption of MPA TDM has been limited by the impracticality of full 0 to 12 hour AUC measurement (AUC0-12), poor correlation between pre-dose MPA concentration and AUC0- 12, ongoing questions regarding the utility of free versus total MPA measurements and lack of evidence correlating MPA exposure with clinical outcomes. Two recent randomized studies evaluating the role of MPA TDM in renal transplant recipients have reported conflicting results. Promising areas of ongoing study include use of Bayesian forecasting to predict MPA dosage and measurement of inosine monophosphate dehydrogenase activity. This review provides an overview of the pharmacokinetics of MMF in solid organ transplantation, and discusses the benefits and limitations of MPA monitoring. Areas that require additional research are identified.
Keyword Mycophenolate mofetil
Organ transplantation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Pharmacy Publications
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Citation counts: TR Web of Science Citation Count  Cited 22 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 05 Jun 2009, 19:49:37 EST by Charna Kovacevic on behalf of School of Pharmacy