ZASTOSOWANIE METOD ANALITYCZNYCH W OZNACZANIU AKTYWNOŚCI DEHYDROGENAZY INOZYNOMONOFOSFORANOWEJ (IMPDH) PODCZAS TERAPII IMMUNOSUPRESYJNEJ

Arkadiusz Kocur; Dorota Marszałek; Tomasz Pawiński

doi:10.56782/pps.13

Published : 2020-08-07

Vol. 18 No. 5 (2020)

USE OF CHROMATOGRAPHIC METHODS FOR INOSINE DEHYDROGENASE ACTIVITY DETERMINATION (IMPDH) IN IMMUNOSUPPRESSIVE THERAPY

Arkadiusz Kocur

Dorota Marszałek

Tomasz Pawiński

DOI: https://doi.org/10.56782/pps.13

Abstract

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.

Keywords:

IMPDH, HPLC, immunosuppressive therapy, mycophenolic acid, PK/PD-model

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Kocur, A., Marszałek, D., & Pawiński, T. (2020). USE OF CHROMATOGRAPHIC METHODS FOR INOSINE DEHYDROGENASE ACTIVITY DETERMINATION (IMPDH) IN IMMUNOSUPPRESSIVE THERAPY. Prospects in Pharmaceutical Sciences, 18(5), 40–49. https://doi.org/10.56782/pps.13

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Arkadiusz Kocur

arkadiusz.kocur@wum.edu.pl

Affiliation:

Zakład Chemii Leków, Wydział Farmaceutyczny, Warszawski Uniwersytet Medyczny, ul. Banacha 1, 02-097 Warszawa Poland

Dorota Marszałek

Affiliation:

Zakład Chemii Leków, Wydział Farmaceutyczny, Warszawski Uniwersytet Medyczny, ul. Banacha 1, 02-097 Warszawa Poland

Tomasz Pawiński

Affiliation:

Zakład Chemii Leków, Wydział Farmaceutyczny, Warszawski Uniwersytet Medyczny, ul. Banacha 1, 02-097 Warszawa Poland