Target Enzyme Activity as a Biomarker for Immunosuppression

Abstract

Pharmacokinetic drug monitoring has been used for many years to relate immunosuppressant dose to drug exposure in vivo. However, this conventional therapeutic drug monitoring of blood immunosuppressant levels may not necessarily predict the pharmacologic effects on immune cells. The direct determination of target enzyme activity (eg, calcineurin activity, inosine-5'-monophospahte dehydrogenase [IMPDH] activity, p70S6 kinase) may help to better assess the individual response to the immunosuppressant. However, its use is limited by the difficulties of the assay systems, which did not allow yet the prospective assessment of these enzymes in larger patient cohorts with the establishment of validated pharmacodynamic drug monitoring. The most progress regarding a robust and reproducible test system has been achieved with the determination of IMPDH activity as a specific pharmacodynamic parameter of mycophenolic acid activity. This recently validated and standardized assay allows the investigation of IMPDH activity in larger clinical studies. Although the determination of target enzyme activity, eg, by the determination of IMPDH activity, holds promise for a more individualized therapy in transplant medicine, more studies are needed to prospectively validate this approach.