ArticlePharmaceutical research2012
In vitro and in vivo metabolic studies of phospho-aspirin (MDC-22).
Article in Pharmaceutical research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
purposeTo investigate the metabolism of phospho-aspirin (PA, MDC-22), a novel anti-cancer and anti-inflammatory agent.
methodsThe metabolism of PA was studied in the liver and intestinal microsomes from mouse, rat and human.
resultsPA is rapidly deacetylated to phospho-salicylic acid (PSA), which undergoes regioselective oxidation to generate 3-OH-PSA and 5-OH-PSA. PSA also can be hydrolyzed to give salicylic acid (SA), which can be further glucuronidated. PA is far more stable in human liver or intestinal microsomes compared to those from mouse or rat due to its slowest deacetylation in human microsomes. Of the five major human cytochrome P450 (CYP) isoforms, CYP2C19 and 2D6 are the most active towards PSA. In contrast to PSA, conventional SA is not appreciably oxidized by the CYPs and liver microsomes, indicating that PSA is a preferred substrate of CYPs. Similarly, PA, in contrast to PSA, cannot be directly oxidized by CYPs and liver microsomes, indicating that the acetyl group of PA abrogates its oxidation by CYPs.
conclusionsOur findings establish the metabolism of PA, reveal significant inter-species differences in its metabolic transformations, and provide an insight into the role of CYPs in these processes.
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