Pharmacodynamic Monitoring of Inosine Monophosphate Dehydrogenase Activity: A Basis For Optimized and Individualized Mycophenolate Mofetil Therapy

In 1896 Gosic isolated for the first time mycophenolic acid (MPA) from Penicillium glaucum.It was subsequently isolated from Penicillium stoloniferum Thom (synonym P. brevi-compactum Dierckx) by Alsberg and Black in 1913 who gave the acid phenolic substance its name mycophenolic acid (MPA).From 1931 to 1933 a series of studies in the biochemistry of micro-organisms was published by Clutterbuck, Raistrick and Oxford of the division of biochemistry from the University of London. These series described in detail the isolation and characterization of MPA. The structure of MPA was finally established in 1952. In the first decades, MPA was eventually found to have antineoplastic, antibacterial, antifungal and antiviral properties and was investigated by a few groups.In 1969, Planterose et al described an effect of MPA most likely to an immunosuppressive effect, and Mitsui et al reported in the same year for the first time the immunosuppressive effect of MPA in mice, at the cellular and humoral levels of antibody formation. In the following years, more and more research was done on the efficacy of MPA as an immunosuppressant. Mycophenolate mofetil (MMF) was developed at Syntex Corporation to be a more bioavailable form of MPA. The first human trials of MMF in kidney recipients were conducted by Sollinger et al, leading to the registration of the pharmaceutical compound as immunosuppressant in 1995.

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