Therapeutic drug monitoring of mycophenolate in adult solid organ transplant patients: an update

ABSTRACT

Introduction: Mycophenolate (MPA) therapeutic drug monitoring (TDM) in adult solid organ transplant recipients was summarized extensively in consensus reports published between 2009 and 2011. Thus, this review provides an update on the science of MPA TDM over the past 5 years.

Areas covered: PubMed and Google Scholar (January 2010-January 2016) were searched; relevant articles from bibliographies of identified articles were extracted for further review. New evidence on TDM-guided dosing in MPA efficacy and toxicity and best approaches for estimating MPA area-under-the-curve for TDM were retrieved.

Expert opinion: Since 2011, little advancement in consensus on MPA TDM has been established for any type of solid organ transplant. Lack of systematic studies validating or further defining MPA’s target range suggests that routine TDM is still unwarranted.

Accurate, precise, and user-friendly limited sampling strategies (LSSs) are available in specific patient populations taking mycophenolate mofetil but not enteric-coated mycophenolate sodium. In absence of outcome data, routine use of LSSs in MPA TDM still cannot be recommended.

Further research should attempt to define factors that modulate MPA’s pharmacokinetics to elucidate their impact on utility of TDM. Future studies should also validate LSSs in larger patient populations and demonstrate benefits of LSSs in improving patient outcomes.

KEYWORDS:

• Mycophenolate
• solid organ transplant
• therapeutic drug monitoring

Article highlights

In the past 5 years, little advancement in consensus on the benefit of MPA TDM has been established for any type of solid organ transplant.

• Most data were collected from kidney transplant recipients, and the majority of the trials studied MPA TDM only in the short-term posttransplant.

• Inconsistencies between studies may be due to the large number of variables (e.g. rejection risk, patient type, concurrent medications, time posttransplant, etc.) typically associated with this patient setting.

• Lack of systematic studies validating the efficacy or further defining the therapeutic MPA target range (AUC 30–60 mg h/L) suggests that TDM still should not be routinely recommended.

• The majority of the new information on LSSs, published in the past 5 years, is still found in kidney patients, and accurate, precise, and user-friendly equations are now available in specific, niche patient populations taking MMF (e.g. steroid-free de novo kidney transplant patients) but not enteric-coated mycophenolate sodium. In the absence of outcome data, routine use of LSSs in MPA TDM still cannot be recommended.

• Further research should attempt to define factors that modulate MPA’s pharmacokinetics to elucidate their impact on utility of TDM. Future studies should also validate LSSs in larger patient populations and demonstrate benefits of LSSs in improving patient outcomes.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.