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Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
08:38

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS

Published on: November 8, 2015

Pharmacodynamic disparities in tacrolimus-treated patients developing cytomegalus virus viremia

Claudia Sommerer1, Martin Zeier, David Czock

  • 1Department of Nephrology, University Hospital, Heidelberg, Germany. claudia.sommerer@med.uni-heidelberg.de

Therapeutic Drug Monitoring
|July 12, 2011
PubMed
Abstract

Insights

Monitoring nuclear factor of activated T cell (NFAT) gene expression in tacrolimus (Tac)-treated patients can help personalize Tac dosing. This approach may identify patients at risk for cytomegalovirus viremia, improving treatment safety and efficacy.

Area of Science:

  • Immunology
  • Pharmacogenomics
  • Transplantation Medicine

Background:

  • The optimal balance between tacrolimus (Tac) efficacy and toxicity is a significant clinical challenge.
  • Monitoring nuclear factor of activated T cell (NFAT)-regulated gene expression offers a potential method to assess individual Tac susceptibility.

Purpose of the Study:

  • To evaluate the utility of quantifying NFAT-regulated gene expression as a tool for monitoring tacrolimus treatment in renal transplant recipients.
  • To correlate NFAT gene expression levels with tacrolimus blood concentrations and clinical outcomes, including cytomegalovirus (CMV) viremia.

Main Methods:

  • Quantitative real-time polymerase chain reaction was used to measure NFAT-regulated gene expression (interleukin-2, interferon-gamma, granulocyte-macrophage colony stimulating factor) in peripheral blood of 73 renal transplant patients.
  • Gene expression was assessed at various time points post-tacrolimus administration (C0, C1.5, C4) and correlated with clinical endpoints over a 1-year period.

Main Results:

  • A significant inverse correlation was observed between individual tacrolimus blood concentrations and the residual expression of NFAT-regulated genes.
  • Patients experiencing cytomegalovirus (CMV) viremia exhibited significantly lower NFAT-regulated gene expression at C1.5 compared to those without viremia, despite similar tacrolimus levels.
  • Residual NFAT-regulated gene expression at C1.5 and C4 was 21% and 35%, respectively.

Conclusions:

  • Monitoring NFAT-regulated gene expression serves as a valuable tool to assess individual responses to tacrolimus therapy in transplant recipients.
  • This method can aid in identifying patients at higher risk for developing CMV viremia, potentially allowing for dose adjustments to optimize safety and minimize toxicity.

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