Pharmacogenetics and immunosuppressive drugs

Abstract

Several candidate genes have been proposed as potential biomarkers for altered pharmacodynamics or pharmacokinetics of immunosuppressive drugs. However, there is usually only limited clinical evidence substantiating the implementation of biomarkers into clinical practice. Testing for thiopurine-S-methyltransferase polymorphisms has been put into routine clinical use quite widely, while the other pharmacogenetic tests are much less frequently used. Relatively good evidence appeared for tacrolimus-related biomarkers; thus, their utilization may be envisaged in the near future. Although the biomarkers related to mycophenolate, sirolimus or other drugs in the therapeutic class may be promising, further research is necessary to provide more robust evidence. The present review focuses on immunosuppressive drugs, excluding biological treatment.

Keywords::

• donor
• immunosuppressants
• pharmacodynamics
• pharmacogenomics
• pharmacokinetics
• recipient

Acknowledgement

Christopher Edward Montoni is acknowledged for editing the manuscript for English language.

Financial & competing interests disclosure

The authors were supported by Charles University Project PRVOUK P25/LF1/2. 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Pharmacogenetics of immunosuppressant drugs has identified a number of candidate predictive biomarkers, most of which, however, need further validation.

• Multiple gene biomarkers are likely to become prevalent in the future.

• Major regulatory agencies have taken several steps toward the implementation of pharmacogenetics during drug development and use.

• Pharmacogenetics of immunosuppressant drugs is, nevertheless, a promising tool that has the potential to become an additional step prior to routinely conducted measures to optimize therapy, which nowadays consists mainly of therapeutic drug monitoring.