Pathway
Paracetamol ADME
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. 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.
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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%). 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.
What the reference databases state
Statements
30 statements
30 statements · 1 reference database · Subject: Paracetamol ADME · Sources: Reactome
- ABCC1 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- ABCC2 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- ABCC3 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- ABCC4 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- ABCC5 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- ABCG2 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- ACY1 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- CNDP2 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- CYP2E1 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- GGT1 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- GGT3P participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- GGT5 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
Show the remaining 18
- GGT6 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- GGT7 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- GSTM1 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- GSTP1 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- GSTT1 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- NAT1 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- NAT2 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- SULT1A1 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- SULT1A3 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- SULT1A4 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- SULT1C4 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- SULT1E1 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- SULT2A1 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- UGT1A1 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- UGT1A10 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- UGT1A6 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- UGT1A9 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only
- UGT2B15 participates in Paracetamol ADMEProteinReactome R-HSA-9753281Inferred only