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27.07.2020 | Review Article | Ausgabe 11/2020

Clinical Pharmacokinetics 11/2020

Maintenance Immunosuppression in Solid Organ Transplantation: Integrating Novel Pharmacodynamic Biomarkers to Inform Calcineurin Inhibitor Dose Selection

Zeitschrift:
Clinical Pharmacokinetics > Ausgabe 11/2020
Autoren:
Abbie D. Leino, Manjunath P. Pai

Abstract

Calcineurin inhibitors, the primary immunosuppressive therapy used to prevent alloreactivity of transplanted organs, have a narrow therapeutic index. Currently, treatment is individualized based on clinical assessment of the risk of rejection or toxicity guided by trough concentration monitoring. Advances in immune monitoring have identified potential markers that may have value in understanding calcineurin inhibitor pharmacodynamics. Integration of these markers has the potential to complement therapeutic drug monitoring. Existing pharmacokinetic–pharmacodynamic (PK–PD) data is largely limited to correlation between the biomarker and trough concentrations at single time points. Immune related gene expression currently has the most evidence supporting PK–PD integration. Novel biomarker-based approaches to pharmacodynamic monitoring including development of enhanced PK–PD models are proposed to realize the full clinical benefit.

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