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Pathway Description
Dextromethorphan metabolism
Homo sapiens
Metabolic Pathway
Created: 2022-03-08
Last Updated: 2023-10-25
Dextromethorphan is an antitussive drug used as a cough suppressant in most over-the-counter cough medication such as cough syrup or drugs such as dayquil. Dextromethorphan is taken orally and digested then from the intestine it is transported by P-glycoprotein into the blood. From the blood it travels to the liver where it is transported in via P-glycoprotein again. Once in the liver it is metabolized on the endoplasmic reticulum membrane into Dextrophan by cytochrome P450 2D6 or cytochrome P450 2C9. Dextrophan is also a drug that functions in a similar way to Dextromethorphan. Dextrophan is metabolized into 3-Hydroxymorphinan by cytochrome P450 3A4 or cytochrome P450 2D6 as well as being metabolized into dextrorphan O-glucuronide by UDP-glucuronosyltransferase 2B4, UDP-glucuronosyltransferase 2B7, UDP-glucuronosyltransferase 2B15, or UDP-glucuronosyltransferase 2B17. 3-Hydroxymorphinan is metabolized into 3-Hydroxymorphinan O-glucuronide by UDP-glucuronosyltransferase 2B4, UDP-glucuronosyltransferase 2B7, UDP-glucuronosyltransferase 2B15, or UDP-glucuronosyltransferase 2B17. Two reactions occur outside the membrane of the endoplasmic reticulum in the cytosol. One is the metabolism of dextrophan into dextrorphan sulfate likely by a sulfotransferase so a sulfate is added onto dextrophan, making it easier to be excreted in the urine. 3-Hydroxymorphinan is also metabolized by a sulfotransferase into 3-Hydroxymorphinan sulfate in the cytosol of the liver.
All of these metabolites leave the liver through P-glycoprotein or another liver transporter for drugs and enter the blood. They then travel to the kidney where 95% is excreted as metabolites, only a small portion remaining as the original dextromethorphan.
References
Dextromethorphan metabolism References
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