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Human In Vitro Suppression as Screening Tool for the Recognition of an Early State of Immune Imbalance
Published on: July 22, 2011
Target enzyme activity as a biomarker for immunosuppression
1Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Pharmacodynamic monitoring of immunosuppressants, like inosine-5'-monophospahte dehydrogenase (IMPDH) activity, offers a more precise way to gauge drug effects than traditional blood level monitoring. This approach promises more individualized therapy for transplant patients.
Area of Science:
- Immunology
- Pharmacology
- Transplant Medicine
Background:
- Conventional pharmacokinetic drug monitoring relates immunosuppressant dose to drug exposure but may not predict pharmacologic effects on immune cells.
- Direct determination of target enzyme activity (e.g., calcineurin, IMPDH, p70S6 kinase) could improve assessment of individual immunosuppressant response.
- Current limitations in assay systems hinder prospective assessment of enzyme activity in large patient cohorts and validated pharmacodynamic drug monitoring.
Purpose of the Study:
- To explore the potential of pharmacodynamic drug monitoring (PDM) for assessing immunosuppressant therapy.
- To highlight the progress in developing robust assays for target enzyme activity, specifically inosine-5 omino-monophospahte dehydrogenase (IMPDH).
- To evaluate the utility of IMPDH activity as a pharmacodynamic parameter for mycophenolic acid.
Main Methods:
- Review of existing literature and assay development for target enzyme activity.
- Focus on the development and validation of a standardized assay for IMPDH activity.
- Discussion of the application of validated assays in clinical studies.
Main Results:
- The determination of IMPDH activity has emerged as a validated and standardized pharmacodynamic parameter for mycophenolic acid.
- This robust assay system allows for the investigation of IMPDH activity in larger clinical studies.
- Significant progress has been made in establishing reproducible test systems for enzyme activity determination.
Conclusions:
- Pharmacodynamic monitoring, particularly IMPDH activity, holds promise for more individualized immunosuppressant therapy in transplant medicine.
- While promising, further prospective studies are needed to fully validate the approach of determining target enzyme activity for personalized treatment.
- The validated IMPDH activity assay represents a significant step towards implementing pharmacodynamic drug monitoring in clinical practice.
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