DECOMPOSITION OF ARTEETHER IN SIMULATED STOMACH ACID YIELDING COMPOUNDS RETAINING ANTIMALARIAL ACTIVITY

In simulated stomach acid (aqueous 0.01 M HCl, 37-degrees-C) beta-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 beta-arteether, whereas compound 1 had approximately 1/10th the activity of beta-arteether. Compound 1 was prepared in sufficient quantities to afford samples for biological evaluation and a complete chemical characterization with H-1- and C-13-NMR and mass spectrometry. While beta-arteether would be somewhat unstable in the stomach, if the drug were administered on an empty stomach (emptying time, almost-equal-to 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.