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Solute carrier family 22 member 1 Multidrug resistance- associated protein 4 Multidrug resistance- associated protein 4 Multidrug resistance- associated protein 4 Multidrug resistance- associated protein 4 Multidrug resistance- associated protein 4 Multidrug resistance- associated protein 4 Multidrug resistance- associated protein 4 ATP-binding cassette sub-family C member 3 Solute carrier family 15 member 1 Cytochrome P450 3A4 Cytochrome P450 2C19 UDP- glucuronosyltransferase 1A3 Unknown Carbonyl reductase [NADPH] 1 UDP- glucuronosyltransferase 1-3 Voriconazole UK-51,060 Voriconazole O-glucuronide derivative (1) UK-215,364 4-Hydroxyvoriconazole 4-Hydroxyvoriconazole 4-O-glucuronide Voriconazole Voriconazole Voriconazole Voriconazole N-Oxide UK-51,060 UK-215,364 4-Hydroxyvoriconazole 4-Hydroxyvoriconazole 4-O-glucuronide Voriconazole O-glucuronide derivative (1) Voriconazole O2 NADPH H+ H2O NADP O2 NADPH H2O O2 NADP Uridine diphosphate glucuronic acid UDP H+ H+ NADPH NADP UDP-D-galacturonate H+ UDP Heme Voriconazole N-Oxide Voriconazole Pathway Urinary excretion Heme Voriconazole N-Oxide is the major metabolite, accounting for 72% of circulating metabolites Less than 2% is excreted unchanged in the urine Intestinal Lumen Epithelial Cell Blood vessel Hepatocyte Blood Vessel Kidney Endoplasmic Reticulum Voriconazole and its metabolites are all excreted through the kidneys Voriconazole is taken orally or injected intravenously. Voriconazole has a 96% bioavailability
Endoplasmic Reticulum SLC22A1 ABCC4 ABCC4 ABCC4 ABCC4 ABCC4 ABCC4 ABCC4 ABCC3 SLC15A1 CYP3A4 CYP2C19 UGT1A3 Unknown CBR1 UGT1A3 Voriconazole UK-51,060 Voriconazole O-glucuronide derivative (1) UK-215,364 4- Hydroxyvoriconazole 4- Hydroxyvoriconazole 4-O-glucuronide Voriconazole Voriconazole Voriconazole Voriconazole N-Oxide UK-51,060 UK-215,364 4- Hydroxyvoriconazole 4- Hydroxyvoriconazole 4-O-glucuronide Voriconazole O-glucuronide derivative (1) Voriconazole Oxygen NADPH Hydrogen Ion Water NADP Oxygen NADPH Water Oxygen NADP Uridine diphosphate glucuronic acid UDP Hydrogen Ion Hydrogen Ion NADPH NADP UDP-D- galacturonate Hydrogen Ion UDP Voriconazole N-Oxide Voriconazole Pathway Urinary excretion