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Improved Delivery Through Biological Membranes. XXXVII. Synthesis and Stability of Novel Redox Derivatives of Naproxen and Indomethacin

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Abstract

Several novel bioreversible redox derivatives of the nonsteroidal antiinflammatory drugs (NSAID) naproxen and indomethacin were synthesized. The stability of these dihydropyridine-NSAID derivatives their synthetic precursors, and predicted products of oxidative metabolism, the corresponding pyridinium salts, was determined in buffer, human and rat blood, and rat organ homogenate. The dihydropyridines exhibited the expected stability profiles in the media examined: oxidation, water addition, and/or ester hydrolysis. The corresponding pyridinium salts were quite stable in biomedia, ester hydrolysis being the primary route of decomposition. The results of this study may be useful in selecting suitable candidates for selective delivery of naproxen and indomethacin across the blood–brain barrier.

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Author notes

  1. Michael J. Phelan

    Present address: United States Army Medical Research Institute of Infectious Diseases (National Research Council Associate), Fort Detrick, Frederick, Maryland

Authors and Affiliations

  1. Center for Drug Design and Delivery, University of Florida, Box J-497, JHMHC, Gainesville, Florida, 32610

    Nicholas Bodor

Authors
  1. Michael J. Phelan
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  2. Nicholas Bodor
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Phelan, M.J., Bodor, N. Improved Delivery Through Biological Membranes. XXXVII. Synthesis and Stability of Novel Redox Derivatives of Naproxen and Indomethacin. Pharm Res 6, 667–676 (1989). https://doi.org/10.1023/A:1015930220855

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  • DOI: https://doi.org/10.1023/A:1015930220855

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