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-arte ether decomposed (half-life, 441 +/- 17 min) to dihydroartemisinin, wh ich subsequently rearranged to a new compound (1) having an endoperoxi de group and an aldehyde group. The in vitro antimalarial activity of dihydroartemisinin is similar to that of beta-arteether, whereas compo und 1 had approximately 1/10th the activity of beta-arteether. Compoun d 1 was prepared in sufficient quantities to afford samples for biolog ical evaluation and a complete chemical characterization with H-1- and C-13-NMR and mass spectrometry. While beta-arteether would be somewha t unstable in the stomach, if the drug were administered on an empty s tomach (emptying time, almost-equal-to 30 min) as a suspension or tabl et, sufficient quantities of intact arteether may reach the small inte stines, where it would be stable and readily absorbed. Its decompositi on products, dihydroartemisinin and 1, may also contribute to the anti malarial activity of the administered drug following oral administrati on.