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Pathway Description
Oxybutynin Metabolism
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2022-04-27
Last Updated: 2023-10-25
Oxybutynin is an antimuscarinic agent used to relax the bladder and prevent the urge to void. It can be taken either orally or intravenously. The bioavailability and the elimination half-life are both increased in the elderly.
When taken orally, oxybutynin enters the intestine and is transported into the intestinal wall by the transporter solute carrier family 15 member 1. It is heavily metabolized by cytochrome P450 3A4 in both the intesine wall and the liver. In the endoplasmic reticulum of the intestine wall oxybutynin is metabolized by cytochrome P450 3A4 into N-desethyloxybutynin, an active metabolite. Oxybutynin is also metabolized into 2-cyclohexyl-2-phenylglycolic acid or phenylcyclohexylglycolic acid also by cytochrome P450 3A4. Both metabolites and the remaining original oxybutynin are transported into the blood by organic cation transporters. N-Desethyloxybutynin is an active metabolite that circulates the blood along with Oxybutynin. N-Desethyloxybutynin is active at muscarinic receptors in the bladder and salavary glands as well.
Oxybutynin travels to the liver where it is transported in via organic cation transporters and metabolized again in the endoplasmic reticulum in the same way it was in the intestine wall. Oxybutynin is heavily cleared by the liver. The majority is metabolized into the inactive metabolite phenylcyclohexylgycolic acid. The metabolites are transported out of the liver and back into the blood where they are eliminated renally. Less than 0.1% is excreted as the active metabolite N-desethyloxybutynin, and less than 0.1% of the dose is excreted as the original oxybutynin. The majority is excreted as the inactive metabolite 2-cyclohexyl-2-phenylglycolic acid.
References
Oxybutynin Metabolism References
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Pubmed: 21212936
Yarker YE, Goa KL, Fitton A: Oxybutynin. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in detrusor instability. Drugs Aging. 1995 Mar;6(3):243-62. doi: 10.2165/00002512-199506030-00007.
Pubmed: 7620236
Douchamps J, Derenne F, Stockis A, Gangji D, Juvent M, Herchuelz A: The pharmacokinetics of oxybutynin in man. Eur J Clin Pharmacol. 1988;35(5):515-20. doi: 10.1007/bf00558247.
Kennelly MJ: A comparative review of oxybutynin chloride formulations: pharmacokinetics and therapeutic efficacy in overactive bladder. Rev Urol. 2010 Winter;12(1):12-9.
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Pubmed: 29126136
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
Hayer M, Bonisch H, Bruss M: Molecular cloning, functional characterization and genomic organization of four alternatively spliced isoforms of the human organic cation transporter 1 (hOCT1/SLC22A1). Ann Hum Genet. 1999 Nov;63(Pt 6):473-82. doi: 10.1017/S0003480099007770.
Pubmed: 11388889
Sakata T, Anzai N, Shin HJ, Noshiro R, Hirata T, Yokoyama H, Kanai Y, Endou H: Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions. Biochem Biophys Res Commun. 2004 Jan 16;313(3):789-93. doi: 10.1016/j.bbrc.2003.11.175.
Pubmed: 14697261
Itoda M, Saito Y, Maekawa K, Hichiya H, Komamura K, Kamakura S, Kitakaze M, Tomoike H, Ueno K, Ozawa S, Sawada J: Seven novel single nucleotide polymorphisms in the human SLC22A1 gene encoding organic cation transporter 1 (OCT1). Drug Metab Pharmacokinet. 2004 Aug;19(4):308-12.
Pubmed: 15499200
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