Plasma and cerebrospinal fluid pharmacokinetic parameters after single-dose administration of intravenous, oral, or rectal acetaminophen

Pain Practice, 05/02/2012

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

Methods

  • 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.

Results

  • 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 μg•h/mL, respectively.
  • No treatment–related adverse events were reported.
  • One subject was replaced because of premature failure of his lumbar spinal catheter.
  • The mean CSF level in the IV group was similar to plasma from 3 to 4 hours and higher from 4 hours on.
  • Absorption phase, variability in plasma, and CSF were greater in PO and PR groups than variability with IV administration.

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