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Pathway Description
Fentanyl Metabolism
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2022-03-22
Last Updated: 2023-10-25
Fentanyl is an opioid that is injected intravenously or intramuscularly where it travels through the blood to the liver. Fentanyl is 80-85% bound to plasma proteins. It is transported into the liver via P-glycoprotein. In the endoplasmic reticulum of a hepatocyte in the liver, 99% of fentanyl is metabolized into norfentanyl via the enzyme Cytochrome P450 3A4. Fentanyl is also predicted by biotransformer to be metabolized into Despropionylfentanyl with the enzyme Cytochrome P450 1A2. It is also predicted by biotransformer to be metabolized into Hydroxyfentanyl by Cytochrome P450 1A2 and that is metabolized into Hydroxynorfentanyl by Cytochrome P450 1A2. All of these metabolites are transported into the blood or the bile by P-glycoprotein. They then travel through the blood to the kidneys through bile to the intestines. 75% is excreted in the urine and 9% is excreted fecally. >7% is excreted as unchanged fentanyl in the urine while >1% is unchanged in the feces.
References
Fentanyl Metabolism References
DePriest AZ, Puet BL, Holt AC, Roberts A, Cone EJ: Metabolism and Disposition of Prescription Opioids: A Review. Forensic Sci Rev. 2015 Jul;27(2):115-45.
Wandel C, Kim R, Wood M, Wood A: Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein. Anesthesiology. 2002 Apr;96(4):913-20.
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
Ikeya K, Jaiswal AK, Owens RA, Jones JE, Nebert DW, Kimura S: Human CYP1A2: sequence, gene structure, comparison with the mouse and rat orthologous gene, and differences in liver 1A2 mRNA expression. Mol Endocrinol. 1989 Sep;3(9):1399-408. doi: 10.1210/mend-3-9-1399.
Pubmed: 2575218
Jaiswal AK, Nebert DW, Gonzalez FJ: Human P3(450): cDNA and complete amino acid sequence. Nucleic Acids Res. 1986 Aug 26;14(16):6773-4. doi: 10.1093/nar/14.16.6773.
Pubmed: 3755823
Quattrochi LC, Pendurthi UR, Okino ST, Potenza C, Tukey RH: Human cytochrome P-450 4 mRNA and gene: part of a multigene family that contains Alu sequences in its mRNA. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6731-5. doi: 10.1073/pnas.83.18.6731.
Pubmed: 3462722
Hsieh KP, Lin YY, Cheng CL, Lai ML, Lin MS, Siest JP, Huang JD: Novel mutations of CYP3A4 in Chinese. Drug Metab Dispos. 2001 Mar;29(3):268-73.
Pubmed: 11181494
Molowa DT, Schuetz EG, Wrighton SA, Watkins PB, Kremers P, Mendez-Picon G, Parker GA, Guzelian PS: Complete cDNA sequence of a cytochrome P-450 inducible by glucocorticoids in human liver. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5311-5. doi: 10.1073/pnas.83.14.5311.
Pubmed: 3460094
Gonzalez FJ, Schmid BJ, Umeno M, Mcbride OW, Hardwick JP, Meyer UA, Gelboin HV, Idle JR: Human P450PCN1: sequence, chromosome localization, and direct evidence through cDNA expression that P450PCN1 is nifedipine oxidase. DNA. 1988 Mar;7(2):79-86. doi: 10.1089/dna.1988.7.79.
Pubmed: 3267210
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