Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Voriconazole Metabolism
Homo sapiens
Metabolic Pathway
Voriconazole is an triazole antifungal medication used to treat serious, invasive fungal infections. It has increased affinity to 14-alpha sterol demethylase which means it is useful against Fluconazole-resistant organisms. Voriconazole is taken either orally or injected intravenously. The bioavailability of voriconazole is 96%. When taken orally it is transported from the intestine into the intestinal epithelial cell possibly via solute carrier family 15 member 1, one of 3 drug transporters into epithelial cells. It is then transported into blood vessels via ATP-binding cassette sub-family C member 3. It is then transported through the blood to the liver where it is transported in by a liver drug transporter like solute carrier family 22 member 1.
On the endoplasmic reticulum membrane Voriconazole is metabolized into Voriconazole N-Oxide by Cytochrome P450 2C9, Cytochrome P450 2C19, Cytochrome P450 3A4, Cytochrome P450 3A5, or Cytochrome P450 3A7, which makes up 72% of metabolites found. Voriconazole N-Oxide is metabolized into a voriconazole related compound (UK-51,060) by an unknown enzyme. That is predicted by biotransformer to be metabolized by Carbonyl reductase [NADPH] 1 into a similar voriconazole related compound (UK-215,364). That is predicted by biotransformer to be metabolized by UDP-glucuronosyltransferase 1-3 into Voriconazole O-glucuronide derivative (1).
Voriconazole also metabolizes into 4-Hydroxyvoriconazole via the enzymes Cytochrome P450 3A4, Cytochrome P450 3A5, or Cytochrome P450 3A7. 4-Hydroxyvoriconazole is predicted by biotransformer to be metabolized by UDP-glucuronosyltransferase 1-3 into 4-Hydroxyvoriconazole 4-O-glucuronide.
Voriconazole and all the metabolites are transported out of the liver and into blood vessels by a transport protein such as multidrug resistance-associated protein 4. They all then travel to the kidney where they are excreted in the urine. Less than 2% of the dose is excreted as unchanged voriconazole. 72% is excreted as the metabolite voriconazole N-oxide.
References
Voriconazole Metabolism References
Murayama N, Imai N, Nakane T, Shimizu M, Yamazaki H: Roles of CYP3A4 and CYP2C19 in methyl hydroxylated and N-oxidized metabolite formation from voriconazole, a new anti-fungal agent, in human liver microsomes. Biochem Pharmacol. 2007 Jun 15;73(12):2020-6. doi: 10.1016/j.bcp.2007.03.012. Epub 2007 Mar 19.
Pubmed: 17433262
Roffey SJ, Cole S, Comby P, Gibson D, Jezequel SG, Nedderman AN, Smith DA, Walker DK, Wood N: The disposition of voriconazole in mouse, rat, rabbit, guinea pig, dog, and human. Drug Metab Dispos. 2003 Jun;31(6):731-41. doi: 10.1124/dmd.31.6.731.
Pubmed: 12756205
Liu, Z., & Liu, K. (2013). The transporters of intestinal tract and techniques applied to evaluate interactions between drugs and transporters. Asian Journal of Pharmaceutical Sciences, 8(3), 151–158. https://doi.org/10.1016/j.ajps.2013.07.020
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings