Abstract
In simulated stomach acid (aqueous 0.01 M HC1, 37°C) β-arteether decomposed (half-life, 441 ± 17 min) to dihydroartemisinin, which subsequently rearranged to a new compound (1) having an endoperoxide group and an aldehyde group. The in vitro antimalarial activity of dihydroartemisinin is similar to that of β-arteether, whereas compound 1 had approximately 1/10th the activity of β-arteether. Compound 1 was prepared in sufficient quantities to afford samples for biological evaluation and a complete chemical characterization with 1H- and 13C-NMR and mass spectrometry. While β-arteether would be somewhat unstable in the stomach, if the drug were administered on an empty stomach (emptying time, ≈30 min) as a suspension or tablet, sufficient quantities of intact arteether may reach the small intestines, where it would be stable and readily absorbed. Its decomposition products, dihydroartemisinin and 1, may also contribute to the antimalarial activity of the administered drug following oral administration.
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Baker, J.K., McChesney, J.D. & Chi, H.T. Decomposition of Arteether in Simulated Stomach Acid Yielding Compounds Retaining Antimalarial Activity. Pharm Res 10, 662–666 (1993). https://doi.org/10.1023/A:1018943329109
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DOI: https://doi.org/10.1023/A:1018943329109