Pharmacodynamic monitoring of mTOR inhibitors

Therapeutic Drug Monitoring
Millán OlgaBrunet Mercè

Abstract

Pharmacodynamic monitoring may complement routine pharmacokinetic monitoring of mTOR inhibitors (mTORi) in an attempt to better guide individualized sirolimus (SRL) or everolimus (EVR) treatment after organ transplantation. This review focuses on current knowledge about pharmacodynamic biomarkers for personalized mTORi therapies.Different strategies have already been employed in the evaluation of the pharmacodynamics of SRL and EVR as a proxy for their effects on the immune response after transplantation. These include measuring p70S6K (70 kDa ribosomal protein S6 kinase) activity, p70S6K phosphorylation (P-p70S6K), or P-S6 protein expression. Compared to Western blot and ELISA, phosphoflow cytometry can detect phosphorylated proteins and differentiate activation-induced changes of signaling molecules inside the cell from unstimulated populations of identical cells in the same sample. Alternatively, in patients receiving a combined therapy, other pharmacodynamic approach is to consider biomarkers such as NFAT residual expression for calcineurin inhibitors, or to evaluate non-specific effects of the drugs such as lymphocyte proliferation, interleukin synthesis, specific peripheral blood T regulatory subsets or lymphocyte surface...Continue Reading

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