ArticleBritish journal of pharmacology2012
The metabolism and pharmacokinetics of phospho-sulindac (OXT-328) and the effect of difluoromethylornithine.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- The Antiangiogenic Effect and Ocular Pharmacology of Novel Modified Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Oxygen-Induced Retinopathy.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2023Article
- Phosphosulindac (OXT-328) prevents and reverses chemotherapy induced peripheral neuropathy in mice.Frontiers in neuroscience · 2023Article
- Review
- NSAIDs and Colorectal Cancer Control: Promise and Challenges.Current pharmacology reports · 2015Article
- Phospho-NSAIDs have enhanced efficacy in mice lacking plasma carboxylesterase: implications for their clinical pharmacology.Pharmaceutical research · 2015Article
- The evolving role of nonsteroidal anti-inflammatory drugs in colon cancer prevention: a cause for optimism.The Journal of pharmacology and experimental therapeutics · 2015Review
- The in vitro metabolism of phospho-sulindac amide, a novel potential anticancer agent.Biochemical pharmacology · 2014Article
- Phospho-sulindac inhibits pancreatic cancer growth: NFATc1 as a drug resistance candidate.International journal of oncology · 2014Article
- Curcumin enhances the lung cancer chemopreventive efficacy of phospho-sulindac by improving its pharmacokinetics.International journal of oncology · 2013Article
- Aerosol administration of phospho-sulindac inhibits lung tumorigenesis.Molecular cancer therapeutics · 2013Article
- Topically applied phospho-sulindac hydrogel is efficacious and safe in the treatment of experimental arthritis in rats.Pharmaceutical research · 2013Article
- In vitro and in vivo metabolic studies of phospho-aspirin (MDC-22).Pharmaceutical research · 2012Article
- 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.Pharmaceutical research · 2012Article
- Development of oseltamivir phosphonate congeners as anti-influenza agents.Journal of medicinal chemistry · 2012Article
- Topical phospho-sulindac (OXT-328) is effective in the treatment of non-melanoma skin cancer.International journal of oncology · 2012Article
- Regioselective oxidation of phospho-NSAIDs by human cytochrome P450 and flavin monooxygenase isoforms: implications for their pharmacokinetic properties and safety.British journal of pharmacology · 2012Article
- Carboxylesterases 1 and 2 hydrolyze phospho-nonsteroidal anti-inflammatory drugs: relevance to their pharmacological activity.The Journal of pharmacology and experimental therapeutics · 2012Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposePhospho-sulindac (PS; OXT-328) prevents colon cancer in mice, especially when combined with difluoromethylornithine (DFMO). Here, we explored its metabolism and pharmacokinetics. EXPERIMENTAL APPROACH: PS metabolism was studied in cultured cells, liver microsomes and cytosol, intestinal microsomes and in mice. Pharmacokinetics and biodistribution of PS were studied in mice. KEY
resultsPS undergoes reduction and oxidation yielding PS sulphide and PS sulphone; is hydrolysed releasing sulindac, which generates sulindac sulphide (SSide) and sulindac sulphone (SSone), all of which are glucuronidated. Liver and intestinal microsomes metabolized PS extensively but cultured cells converted only 10% of it to PS sulphide and PS sulphone. In mice, oral PS is rapidly absorbed, metabolized and distributed to the blood and other tissues. PS survives only partially intact in blood; of its three major metabolites (sulindac, SSide and SSone), sulindac has the highest C(max) and SSone the highest t(1/2) ; their AUC(0-24h) are similar. Compared with conventional sulindac, PS generated more SSone but less SSide, which may contribute to the safety of PS. In the gastroduodenal wall of mice, 71% of PS was intact; sulindac, SSide and SSone together accounted for <30% of the total. This finding may explain the lack of gastrointestinal toxicity by PS. DFMO had no effect on PS metabolism but significantly reduced drug level in mouse plasma and other tissues. CONCLUSIONS AND IMPLICATIONS: Our findings establish the metabolism of PS define its pharmacokinetics and biodistribution, describe its interactions with DFMO and largely explain its gastrointestinal safety.
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