USE OF CHROMATOGRAPHIC METHODS FOR INOSINE DEHYDROGENASE ACTIVITY DETERMINATION (IMPDH) IN IMMUNOSUPPRESSIVE THERAPY
DOI:
https://doi.org/10.56782/pps.13Keywords:
IMPDH, HPLC, immunosuppressive therapy, mycophenolic acid, PK/PD-modelAbstract
Inosine-5′-monophosphate dehydrogenase (IMPDH) plays a key role in the de novo pathway synthesis and metabolism of the purine nucleotides, especially in the B and T lymphocyte cells. There are two isoforms of this enzyme (IMPDH I and IMPDH II) encoded by different genes, located on two different chromosomes. The IMPDH II isoform is dominant over the IMPDH I in rapidly proliferating lymphocytic cells. For that reason, the clinical significance of IMPDH is most important according to the immunosuppressive and anticancer therapy. The widely used immunosuppressant agents in post-transplantation therapy are mycophenolates (morpholinoethyl ester of mycophenolic acid and mycophenolate sodium) which are strong, non-competitive and reversible inhibitors of IMPDH. It should be noted that concentration of that agents must be monitored in the blood, due to narrow therapeutic range. The following literature review presents methods which may be used in determination of IMPDH activity and should be associated with the PK/PD (pharmacokinetic-pharmacodynamic) models. The work compares the methods developed over the last 25 years in terms of their usefulness and speed of performance for the determination in diagnostic laboratory. Special attention has been paid using chromatographic methods due to its specificity and recognizing it as “gold standard” in measurment of IMPDH activity as biomarkers.
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