Regioselective oxidation of phospho‐NSAIDs by human cytochrome P450 and flavin monooxygenase isoforms: implications for their pharmacokinetic properties and safety

  title={Regioselective oxidation of phospho‐NSAIDs by human cytochrome P450 and flavin monooxygenase isoforms: implications for their pharmacokinetic properties and safety},
  author={Gang Xie and Chi Chun Wong and Ka-Wing Cheng and Liqun Huang and Panayiotis Constantinides and Basil Rigas},
  journal={British Journal of Pharmacology},
  • G. Xie, C. Wong, B. Rigas
  • Published 1 September 2012
  • Biology, Medicine
  • British Journal of Pharmacology
Phospho‐ibuprofen (MDC‐917) and phospho‐sulindac (OXT‐328) are highly effective in cancer and arthritis treatment in preclinical models. Here, we investigated their metabolism by major human cytochrome P450s (CYPs) and flavin monooxygenases (FMOs). 
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Comparative in vitro metabolism of phospho-tyrosol-indomethacin by mice, rats and humans.
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  • I. Phillips, E. Shephard
  • Biology, Chemistry
    Xenobiotica; the fate of foreign compounds in biological systems
  • 2019
Genetic variants of human flavin-containing monooxygenase 3 (FMO3) have been associated with a number of disorders, but additional studies are needed to confirm or refute such associations.
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Identification of roles for FMO1 and FMO5 in endogenous metabolism has implications for drug therapy and initiates an exciting area of research.
Recent Developments in Chimeric NSAIDs as Safer Anti‐Inflammatory Agents
This review deals with approaches and strategies that have been employed in the last two decades and are being used currently in the design and development of safer NSAIDs.
Relative Expression of Mouse Udp-Glucuronosyl Transferase 2b1 Gene in The Livers, Kidneys, And Hearts: The Influence of Nonsteroidal Anti-Inflammatory Drug Treatment.
It was found that the mouse ugt2b1 gene was mainly expressed in the liver, as 14-day administration of different NSAIDs caused alterations in the expression of this gene, which may influence the metabolism of xenobiotic and endogenous compounds.


The metabolism and pharmacokinetics of phospho‐sulindac (OXT‐328) and the effect of difluoromethylornithine
Phospho‐sulindac prevents colon cancer in mice, especially when combined with difluoromethylornithine (DFMO) and here, its metabolism and pharmacokinetics are explored.
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Some distinctions between flavin-containing and cytochrome P450 monooxygenases.
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    Biochemical and biophysical research communications
  • 2005
The novel phospho‐non‐steroidal anti‐inflammatory drugs, OXT‐328, MDC‐22 and MDC‐917, inhibit adjuvant‐induced arthritis in rats
Three novel modified NSAIDs are evaluated for the anti‐inflammatory efficacy and safety in rheumatoid arthritis: phospho‐aspirin,ospho‐ibuprofen and phospho-sulindac.
Phospho-sulindac (OXT-328), a novel sulindac derivative, is safe and effective in colon cancer prevention in mice.
BACKGROUND & AIMS Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective cancer chemopreventive agents. However, chronic administration of NSAIDs is associated with significant side effects,
Phospho-Ibuprofen (MDC-917) Is a Novel Agent against Colon Cancer: Efficacy, Metabolism, and Pharmacokinetics in Mouse Models
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