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APAP ADME

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-9753281

PubChem

R-HSA-9753281

Description

Paracetamol (APAP, aka acetaminophen or N-acetyl-p-aminophenol) is an analgesic drug used for to treat mild to moderate pain and as an antipyretic agent. It is one of the most widely used drugs in the world and is available alone or in combination with other drugs for pain relief, fever and allergy. It is thought to act through the inhibition of cyclooxygenases 1 and 2 (Graham et al. 2013, Esh et al. 2021). Paracetamol is generally safe at therapeutic doses but in overdose cases, it causes mitochondrial dysfunction and centrilobular necrosis in the liver which can lead to death.

APAP has a high oral bioavailability (~88%), is well absorbed and reaches peak blood concentrations after 90 minutes after ingestion. APAP binds plasma proteins to a small extent and has a plasma half-life of 1.5-3 hours. Most of the drug is eliminated by glucuronidate and sulfate conjugation (~55% and ~30% respectively) in the liver or as unchanged drug (~5%) (Forrest et al. 1982). A small amount (5-15%) is oxidised to the reactive metabolite N-acetyl-para-benzoquinone imine (NAPQI). NAPQI is usually detoxified by binding to liver glutathione but in overdose cases, glutathione is depleted and NAPQI instead, binds to sulfhydryl groups on proteins, leading to liver damage. ABCC2, ABCC3, ABCC4 and ABCG2 transporters mediate the efflux of APAP metabolites out of cells (McGill & Jaeschke 2013).

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying entries **1 - 10** of 18 in total

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UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
A6NGU5	Putative glutathione hydrolase 3 proenzyme	GGT3 GGT3P	view
O15438	ATP-binding cassette sub-family C member 3	ABCC3 CMOAT2 MLP2 MRP3	view
O15439	ATP-binding cassette sub-family C member 4	ABCC4 MOATB MRP4	view
O15440	ATP-binding cassette sub-family C member 5	ABCC5 MRP5	view
O60656	UDP-glucuronosyltransferase 1A9	GNT1 UGT1 UGT1A9	view
P11245	Arylamine N-acetyltransferase 2	AAC2 NAT2	view
P19224	UDP-glucuronosyltransferase 1A6	GNT1 UGT1 UGT1A6	view
P19440	Glutathione hydrolase 1 proenzyme	GGT GGT1	view
P22309	UDP-glucuronosyltransferase 1A1	GNT1 UGT1 UGT1A1	view
P33527	Multidrug resistance-associated protein 1	ABCC1 MRP MRP1	view

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