The metabolism and pharmacokinetics of phospho‐sulindac (OXT‐328) and the effect of difluoromethylornithine

@article{Xie2012TheMA,
  title={The metabolism and pharmacokinetics of phospho‐sulindac (OXT‐328) and the effect of difluoromethylornithine},
  author={Gang Xie and Ting Nie and G G Mackenzie and Y Sun and L. Huang and Nengtai Ouyang and Ninche Alston and C. Zhu and Onika T. Murray and Panayiotis Constantinides and Levy Kopelovich and Basil Rigas},
  journal={British Journal of Pharmacology},
  year={2012},
  volume={165}
}
  • G. Xie, T. Nie, B. Rigas
  • Published 1 April 2012
  • Medicine, Biology, Chemistry
  • British Journal of Pharmacology
BACKGROUND AND PURPOSE Phospho‐sulindac (PS; OXT‐328) prevents colon cancer in mice, especially when combined with difluoromethylornithine (DFMO). Here, we explored its metabolism and pharmacokinetics. 
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21 Citations
Background Citations
13
Methods Citations
3
Results Citations
2

21 Citations

Regioselective oxidation of phospho‐NSAIDs by human cytochrome P450 and flavin monooxygenase isoforms: implications for their pharmacokinetic properties and safety
TLDR
Phospho‐ibuprofen and phospho‐sulindac metabolism by major human cytochrome P450s (CYPs) and flavin monooxygenases (FMOs) is investigated.
The in vitro metabolism of phospho-sulindac amide, a novel potential anticancer agent.
The ocular pharmacokinetics and biodistribution of phospho‐sulindac (OXT‐328) formulated in nanoparticles: Enhanced and targeted tissue drug delivery
Aerosol Administration of Phospho-Sulindac Inhibits Lung Tumorigenesis
TLDR
It is found that administration by inhalation delivered high levels of phospho-sulindac to the lungs and minimized its hydrolysis to less active metabolites and was highly effective in inhibiting lung tumorigenesis and significantly improved the survival of mice bearing orthotopic A549 xenografts.
Phospho-Sulindac (OXT-328) Inhibits the Growth of Human Lung Cancer Xenografts in Mice: Enhanced Efficacy and Mitochondria Targeting by its Formulation in Solid Lipid Nanoparticles
TLDR
The results show that SLN-PS is efficacious in suppressing the growth of lung cancer and merits further evaluation, suggesting that it specifically induced oxidative stress in tumors.
Development of oseltamivir phosphonate congeners as anti-influenza agents.
TLDR
Oseltamivir phosphonic acid, its mono methyl ester, guanidino-tamiphosphor, and its monoethyl ester are potent inhibitors of influenza neuraminidases that inhibit the replication of influenza viruses at low nanomolar to picomolar levels, and significantly protect mice from infection with lethal doses of influenza virus when orally administered with 1 mg/kg or higher doses.
Carboxylesterases 1 and 2 Hydrolyze Phospho-Nonsteroidal Anti-Inflammatory Drugs: Relevance to Their Pharmacological Activity
TLDR
Results show that carboxylesterase mediates that metabolic inactivation of phospho-NSAIDs, and the inhibition of carboxyleterases improves the efficacy of phosphate- NSAIDs in vitro and in vivo.
Curcumin enhances the lung cancer chemopreventive efficacy of phospho-sulindac by improving its pharmacokinetics
TLDR
Results show that curcumin substantially improves the pharmacokinetics of PS leading to synergistic inhibition of the growth of human lung cancer xenografts, representing a promising drug combination.
Recent Developments in Chimeric NSAIDs as Safer Anti‐Inflammatory Agents
TLDR
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.
NSAIDs: Old Acquaintance in the Pipeline for Cancer Treatment and Prevention─Structural Modulation, Mechanisms of Action, and Bright Future.
TLDR
The most recent outcomes for the treatment and prevention of different types of cancers for several NSAIDs alone or in combination with current chemotherapeutic drugs are reported and an extensive review of the most promising structural modifications is reported.
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References

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TLDR
P-S/DFMO is an efficacious drug combination for colon cancer prevention and also show the safety of P-S, which may overcome the limiting side effects of conventional sulindac.
Phospho-sulindac (OXT-328), a novel sulindac derivative, is safe and effective in colon cancer prevention in mice.
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  • Biology, Chemistry
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TLDR
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