Paracetamol 1.0% w/v · Infusion

The precise mechanism of the analgesic and antipyretic properties of acetaminophen is not established but is thought to primarily involve central actions.

Distribution — The pharmacokinetics of acetaminophen have been studied in patients and healthy subjects up to 60 years old. The pharmacokinetic profile of acetaminophen has been demonstrated to be dose proportional in adults following administration of single-doses of 500, 650, and 1,000 mg.

The maximum concentration (C max) occurs at the end of the 15 minute intravenous infusion of acetaminophen. Compared to the same dose of oral acetaminophen, the C maxfollowing administration of acetaminophen is up to 70% higher, while overall exposure (area under the concentration time curve [AUC]) is very similar.

Pharmacokinetic parameters of acetaminophen (AUC, C max, terminal elimination half-life [T½], systemic clearance [CL], and volume of distribution at steady state [V ss]) following administration of a single intravenous dose of 15 mg/kg in children and adolescents and 1,000 mg in adults are summarized in Table 5.

The concentrations of acetaminophen observed in neonates greater than 32 weeks gestational age at birth treated with 12.5 mg/kg dose are similar to infants, children and adolescents treated with a 15 mg/kg dose, and similar to adults treated with a 1,000 mg dose.

At therapeutic levels, binding of acetaminophen to plasma proteins is low (ranging from 10% to 25%). Acetaminophen appears to be widely distributed throughout most body tissues except fat.

Metabolism and Excretion — Acetaminophen is primarily metabolized in the liver by first-order kinetics and involves three principal separate pathways: Conjugation with glucuronide, conjugation with sulfate, and oxidation via the cytochrome P450 enzyme pathway, primarily CYP2E1, to form a reactive intermediate metabolite (N-acetyl-p-benzoquinone imine or NAPQI). With therapeutic doses, NAPQI undergoes rapid conjugation with glutathione and is then further metabolized to form cysteine and mercapturic acid conjugates.

Acetaminophen metabolites are mainly excreted in the urine. Less than 5% is excreted in the urine as unconjugated (free) acetaminophen and more than 90% of the administered dose is excreted within 24 hours.