对乙酰氨基酚的 ADME 特性
中文名称
通路描述
对乙酰氨基酚（APAP，又称乙酰苯胺或 N-乙酰 -p-氨基苯酚）是一种用于治疗轻度至中度疼痛和作为退烧药的镇痛药。它是世界上使用最广泛的药物之一，单独或与另一种药物组合使用以缓解疼痛、退烧和过敏。它被认为通过抑制环氧化酶 1 和 2（Graham et al. 2013, Esh et al. 2021）发挥作用。在治疗剂量下，对乙酰氨基酚通常安全，但在过量情况下，它会导致肝脏线粒体功能障碍和肝中央坏死，可能导致死亡。
英文描述
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 (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).
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).
所含基因
30 个基因