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Multidrug resistance associated protein UDP- glucuronosyltransferase 2B7 Dihydroartemisinin (DHA) Heme Dihydroartemisinin (DHA) Dihydroartemisinin (DHA) Dihydroartemisinin (DHA) Dihydroartemisinin (DHA) Artemether O2 NADH Formaldehyde NAD H2O Uridine diphosphate glucuronic acid Dihydroartemisinin glucuronide Uridine 5'-diphosphate Superoxide Hydroxyl Radical UDP- glucuronosyltransferase 1-9 Cytochrome P450 3A4 Cytochrome P450 3A5 Endoplasmic Reticulum Hepatocyte Artemether is readily absorbed into the body and goes through first pass metabolism. Artemether is then broken down within the hepatocyte by cytochrome P450 into its active metabolite dihydroartemisinin (DHA). DHA is then further broken down into dihydroartemisinin glucuronide by UDP-glucuronosyltransferase. This now becomes an inactive metabolite that is then eliminated from the body by excretion of bile. DHA interacts with the heme in the parasitic food vacoule causing the production of radical species that damages the parasite Malaria Cell Cytosol Vacuole Erythrocyte
Vacuole MRP3 UGT2B7 Dihydroartemisinin (DHA) Heme Dihydroartemisinin (DHA) Dihydroartemisinin (DHA) Dihydroartemisinin (DHA) Dihydroartemisinin (DHA) Artemether Oxygen NADH Formaldehyde NAD Water Uridine diphosphate glucuronic acid Dihydroartemisinin glucuronide Uridine 5'-diphosphate Superoxide Hydroxyl Radical UGT1A9 CYP3A4 CYP3A5
MRP3 UGT2B7 DHAMN Heme DHAMN DHAMN DHAMN DHAMN Artemet O2 NADH Formol NAD H2O UDPGlcA Alaxin UDP O2(-) Hyd Rad UGT1A9 CYP3A4 CYP3A5 Endoplasmic Reticulum Hepatocyte Artemether is readily absorbed into the body and goes through first pass metabolism. Artemether is then broken down within the hepatocyte by cytochrome P450 into its active metabolite dihydroartemisinin (DHA). DHA is then further broken down into dihydroartemisinin glucuronide by UDP-glucuronosyltransferase. This now becomes an inactive metabolite that is then eliminated from the body by excretion of bile. DHA interacts with the heme in the parasitic food vacoule causing the production of radical species that damages the parasite