Therapeutic drug monitoring in kidney and liver transplantation: current advances and future directions

ABSTRACT

Introduction

Immunosuppressive drugs (ISD) present a narrow therapeutic window and extremely high inter- and intra-individual pharmacokinetic variability, which complicates their use in solid organ transplant recipients. In order to find a narrow appropriate equilibrium for each patient with the aim of maintaining clinical efficacy and reducing the risk of adverse drug reactions, a complex both clinical and biological monitoring is required, in particular through the use of therapeutic drug monitoring (TDM).

Area covered

This review provides an overview of the available information on the relationship between exposure to immunosuppressive drugs and their efficacy and/or toxicity in kidney and liver transplantation. The aim of the review is to describe the pharmacodynamic/pharmacokinetic relationship that exists for immunosuppressive drugs, to summarize the studies that assess the value of TDM for these drugs in clinical practice, and to present the target and monitoring strategies aimed at optimizing patient immunosuppression, which could help to take a step forward in the field of solid organ transplant patient care.

Expert opinion

To improve the care of transplant patients, several TDM innovations can be pursued by investigators. Among these, the development of microsampling methods for TDM or the combination of pharmacodynamic biomarkers with ISD exposure measurements appear to be relevant strategies.

KEYWORDS:

• Calcineurin inhibitor
• immunosuppressant
• microsampling
• mTOR inhibitor
• mycophenolic acid
• organ transplantation
• drug monitoring

Article highlights

• This review summarizes the state-of-the-art of therapeutic drug monitoring (TDM) of immunosuppressive drugs in kidney and liver transplantation.

• This review provides updated exposure target for the immunosuppressive drugs used in the field.

• Notably, this review highlights the interest in area under the curve monitoring for tacrolimus and mycophenolic acid.

• The perspective in the field of immunosuppressive drugs TDM relies on monitoring net state immunosuppression and using microsampling approaches for immunosuppressive drugs TDM.

• Finally, this review promotes the research in the field of combining both pharmacodynamic and pharmacokinetic evaluation to provide an individualized therapeutic strategy in solid organ transplantation.

Declaration of interest

F Lemaitre received research grants (paid to institution) from Chiesi, Astellas, and Sandoz and fees to attend scientific meetings from Chiesi and Pfizer. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.