Analgesic + antipyretic action without meaningful peripheral anti-inflammatory or antiplatelet effect. Central arachidonic acid cascade COX-2 inhibition is one hypothesis; additional contribution from active metabolite AM404 (formed in CNS by FAAH) acting on endocannabinoid system + TRPV1 systems. ~90% of dose conjugated (glucuronide + sulfate); ~5% oxidised by CYP2E1 to the hepatotoxic metabolite NAPQI, normally detoxified by glutathione — overwhelmed in overdose or glutathione-depleted states (chronic alcohol, fasting, malnutrition). nac is the antidote via glutathione repletion.
Half-Life (t½)
PO: 2.5h, IV: 2.5h
Dosing Guidelines
PO: Typical 667 mg (Range: 500–1000 mg)
IV: Typical 667 mg (Range: 500–1000 mg)
Target Organ Systems
digestive
immune-hematologic
Interactions
Warfarin (caution): Chronic APAP ≥2 g/d raises INR modestly (mechanism unclear — possibly CYP2C9 substrate competition). Dose-related; intermittent low-dose use is generally safe. [Holbrook 2005]
Alcohol (major): Chronic alcohol induces CYP2E1 → more NAPQI + depleted glutathione → hepatotoxicity at lower APAP doses. Limit APAP to ≤2 g/d in heavy drinkers. [Zimmerman 1995]
Ibuprofen / NSAIDs (synergistic): Complementary mechanisms — APAP + ibuprofen outperforms either alone for post-op/dental pain.