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Chaperoning the Immunosuppressant Mycophenolic Acid through the Gastrointestinal Tract: a Role for Copper

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Abstract

Mycophenolic acid (MPA) is a frontline immunosuppressant that limits rejection of transplanted organs. Optimal use of this drug is hampered by gastrointestinal adverse events that are thought to be triggered during the absorption phase. These events have a negative impact on graft and patient survival. Previous work has suggested that similar gastrointestinal adverse events observed with non-steroidal antiinflammatory use can be limited by delivering the drug as a copper complex. We have recently shown that MPA is able to bind copper ions to form [Cu(MPA)2(H2O)2]. We report here that this complex is retained in a solvent that mimics the low pH, high salt environment of the upper gastrointestinal tract, suggesting that copper chelation may be a useful way to modulate and control MPA absorption. In an organic solvent, the complex can be modified using the physiologically relevant ligand imidazole to form [CuMPA(imid)3], however this complex is not retained in low pH conditions.

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Acknowledgments

This work was supported by a University of Queensland Early Career Researcher grant (CEJ).

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Authors and Affiliations

  1. The School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Brisbane, 4072, Australia

    Alison C. Badrick & Christopher E. Jones

  2. The Centre for Magnetic Resonance, The University of Queensland, St. Lucia, Brisbane, 4072, Australia

    Graeme R. Hanson

  3. The Queensland Brain Institute, The University of Queensland, St. Lucia, Brisbane, 4072, Australia

    Christopher E. Jones

Authors
  1. Alison C. Badrick
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  2. Graeme R. Hanson
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  3. Christopher E. Jones
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Correspondence to Christopher E. Jones.

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Badrick, A.C., Hanson, G.R. & Jones, C.E. Chaperoning the Immunosuppressant Mycophenolic Acid through the Gastrointestinal Tract: a Role for Copper. Appl Magn Reson 36, 231–236 (2009). https://doi.org/10.1007/s00723-009-0021-7

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  • DOI: https://doi.org/10.1007/s00723-009-0021-7

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