Pharmacokinetics And Metabolism

Oral acetaminophen has excellent bioavailability. Peak plasma concentrations occur within 30-60 minutes and the t122 in plasma is -2 hours. Binding of the drug to plasma proteins is less than with other NSAIDs. Some 90-100% of the drug may be recovered in the urine within the first day at therapeutic dosing, primarily after hepatic conjugation with glucuronic acid (-60%), sulfuric acid (-35%), or cysteine (-3%); small amounts of hydroxylated and deacetylated metabolites also have been detected (Table 26-1). Children have less capacity for glucuronidation of the drug than do adults. A small proportion of acetaminophen undergoes CYP-mediated N-hydroxylation to form N-acetyl-p-benzoquinoneimine (NAPQI), a highly reactive intermediate (see below).

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