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Published on: April 16, 2021
Effect of mycophenolic acid glucuronide on inosine monophosphate dehydrogenase activity
1Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, USA.
Abstract:
Mycophenolic acid glucuronide (MPAG) inhibition kinetics were evaluated using purified recombinant human type II inosine monophosphate dehydrogenase (IMPDH). MPAG inhibitory concentrations (IC50) were found to be 532- to 1022-fold higher than those for MPA. As expected, according to tight-binding inhibitor kinetics, mycophenolic acid (MPA) IC50 values increased as IMPDH concentrations increased, whereas IC50 values for xanthosine monophosphate (competitive IMPDH inhibitor used as control), an inhibitor known not to be tight binding, remained independent of enzyme concentration. Although MPAG exhibited only weak inhibition of IMPDH activity, in comparison with MPA, IC50 values increased with increasing enzyme concentration. The presence of trace quantities of MPA (0.2% on a molar basis) in the MPAG preparation, detected by high-performance liquid chromatography analysis, could account for this observation. These data support the proposal that MPAG is a pharmacologically inactive metabolite of MPA.
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