Document Detail


Plasma and Cerebrospinal Fluid Pharmacokinetic Parameters After Single-Dose Administration of Intravenous, Oral, or Rectal Acetaminophen.
MedLine Citation:
PMID:  22524979     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 (AUC(0-6) ) 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.
Authors:
Neil K Singla; Cherri Parulan; Roselle Samson; Joel Hutchinson; Rick Bushnell; Evelyn G Beja; Robert Ang; Mike A Royal
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-24
Journal Detail:
Title:  Pain practice : the official journal of World Institute of Pain     Volume:  -     ISSN:  1533-2500     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101130835     Medline TA:  Pain Pract     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Lotus Clinical Research, LLC. Pain Practice © 2012 World Institute of Pain.
Affiliation:
Lotus Clinical Research LLC, Pasadena, California, U.S.A. Huntington Memorial Hospital, Pasadena, California, U.S.A. Cadence Pharmaceuticals, Inc., San Diego, California, U.S.A.
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