Sep. 1, 2012

Plasma and Cerebrospinal Fluid Pharmacokinetic Parameters After Single-Dose Administration of Intravenous, Oral, or Rectal Acetaminophen


This is the first study to compare plasma and cerebrospinal fluid (CSF) pharmacokinetics of intravenous (IV), oral (PO), or rectal (PR) formulations of acetaminophen.

Healthy male subjects (N = 6) were randomized to receive a single dose of IV (OFIRMEV; Cadence) 1,000 mg (15 minute infusion), PO (2 Tylenol 500 mg caplets; McNeil Consumer Healthcare), or PR acetaminophen (2 Feverall 650 mg suppositories; Actavis) with a 1-day washout period between doses. The 1,300 mg PR concentrations were standardized to 1,000 mg. Acetaminophen plasma and CSF levels were obtained at T0, 0.25, 0.5, 0.75, 1, 2, 3, 4, and 6 hours.

IV acetaminophen showed earlier and higher plasma and CSF levels compared with PO or PR administration.

CSF bioavailability over 6 hours (AUC0–6) for IV, PO, and PR 1 g was 24.9, 14.2, and 10.3 lgÆh/mL, respectively.

No treatment-related adverse events were reported.

These results demonstrate that earlier and greater CSF penetration occurs as a result of the earlier and higher plasma peak with IV administration compared with PO or PR.

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