Acetaminophen

pharmacological · digestive · immune-hematologic · Oral · IV

Acetaminophen. Analgesic + antipyretic action without meaningful peripheral anti-inflammatory or antiplatelet effect. Central arachidonic acid… Oral half-life 2.5 h.

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.

PK: the saturable architecture is RIGHT and is kept — sulphation is saturable with a Michaelis constant of 14.66 mg/L, inside the therapeutic range, while glucuronidation sits about seventy times above peak concentrations and is legitimately linear. But all three values are DERIVED, NOT QUOTED: they reproduce exactly from the abstract millimolar figures only under a 70 kg weight and a 60 L volume the paper never states, and that volume was itself unsourced, making the derivation circular. The volume is now sourced independently (50.8 L, PMID:28419483) and the maximum-rate field keeps a unit caveat, since the quantity is mg/L/h rather than a rate constant. F 0.822 replaces an unsourced 0.88. The half-life is re-sourced to a stated range endpoint and is consistent with what the saturable pair already implies, about 2.34 h — and it is in any case INERT, because the solver ignores a first-order rate on a saturable route. THE PAPER THIRD PATHWAY IS NOT MODELLED: the glutathione route that matters in overdose. A reference on this record was a WARFARIN review.

Pharmacokinetics

Related compounds

Sources: PMID:6347057, PMID:15911722, PMID:7657281, PMID:28419483, PMID:1487229, PMID:7002186