Disclosures: Neil K. Singla: Speaker Bureau, Research Support, Consultant; Cherri Parulan and Roselle Samson: Research Support; Joel Hutchinson, Rick Bushnell and Evelyn G. Beja: No conflicts to report; Robert Ang and Mike A. Royal: Shareholder and employee of Cadence Pharmaceuticals, Inc. Institutional Review Board that approved the study: Aspire IRB, 9340 Fuerte Dr, Suite 210, La Mesa, CA 91941, U.S.A.
Plasma and Cerebrospinal Fluid Pharmacokinetic Parameters After Single-Dose Administration of Intravenous, Oral, or Rectal Acetaminophen
Version of Record online: 24 APR 2012
© 2012 Lotus Clinical Research, LLC. Pain Practice © 2012 World Institute of Pain
Volume 12, Issue 7, pages 523–532, September 2012
How to Cite
Singla, N. K., Parulan, C., Samson, R., Hutchinson, J., Bushnell, R., Beja, E. G., Ang, R. and Royal, M. A. (2012), Plasma and Cerebrospinal Fluid Pharmacokinetic Parameters After Single-Dose Administration of Intravenous, Oral, or Rectal Acetaminophen. Pain Practice, 12: 523–532. doi: 10.1111/j.1533-2500.2012.00556.x
Correction added on 18 May 2012, after first online publication: The ‘Financial Support’ statement was added to the ‘Acknowledgements’ section.
- Issue online: 6 SEP 2012
- Version of Record online: 24 APR 2012
- Submitted: January 23, 2012; Accepted: March 5, 2012
- drug administration routes
Background: This is the first study to compare plasma and cerebrospinal fluid (CSF) pharmacokinetics of intravenous (IV), oral (PO), or rectal (PR) formulations of acetaminophen.
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.
Conclusions: 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.