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Effect of confounding factors on a phospho-flow assay of ribosomal S6 protein for therapeutic drug monitoring of the mTOR-inhibitor everolimus in heart transplanted patients
Authors:Maja-Theresa Dieterlen  Katja John  Susanne Haase  Jens Garbade  Attila Tarnok  Friedrich W Mohr
Institution:1. HELIOS Clinic, Department of Cardiac Surgery, University Hospital Leipzig, Heart Center, Leipzig, Germany;2. HELIOS Clinic, Department of Pediatric Cardiology, University Hospital Leipzig, Heart Center, Leipzig, Germany
Abstract:Context: Several assays of monitoring immune cell function have been developed to enhance therapeutic drug monitoring.

Objective: An in vitro-validated whole-blood assay of phosphorylated ribosomal protein S6 (pS6RP) was evaluated for confounders to monitor the mTOR-inhibitor everolimus (ERL).

Materials and methods: Whole blood samples from 87 heart transplant recipients were analyzed for pS6RP-expression in CD3-positive T-cells by phospho-flow analysis.

Results: ERL blood concentration, laboratory parameters, co-medications, demographic and clinical data were reviewed.

Conclusion: Evaluating the pS6RP-assay revealed that pS6RP is influenced by cyclosporine A (CsA) blood concentration, duration of ERL treatment, co-medication with thiazide diuretics and different metabolic parameters.

Keywords:S6 ribosomal protein  everolimus  phospho-flow  mTOR-inhibitor
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