Lack of effect of cimetidine on acetaminophen disposition in humans.

Journal Article (Journal Article)

The effect of cimetidine administration on the disposition of acetaminophen was evaluated in seven men and six women. One gram of acetaminophen was administered to each volunteer after an overnight fast on two occasions in a balanced crossover design with and without cimetidine, 300 mg every 6 hours beginning 50 hours before acetaminophen administration and continuing for 22 hours after. N-Acetylcysteine was administered on both occasions when acetaminophen was ingested to protect against glutathione depletion. Blood samples were collected serially for 12 hours after acetaminophen administration, and total urine volume was collected for 24 hours. Fractional clearances of acetaminophen through renal and metabolic routes (sulfation, glucuronidation, 3-hydroxylation, and glutathione conjugate formation) were not altered by cimetidine administration. Studies in microsomes prepared from two human organ donors indicated that cimetidine inhibited acetaminophen reactive metabolite formation noncompetitively, with Ki values of 0.35 mmol/L and 0.32 mmol/L for the respective livers, which is 5 to 10 times the putative cimetidine concentration required for therapeutic effect.

Full Text

Duke Authors

Cited Authors

  • Slattery, JT; McRorie, TI; Reynolds, R; Kalhorn, TF; Kharasch, ED; Eddy, AC

Published Date

  • November 1989

Published In

Volume / Issue

  • 46 / 5

Start / End Page

  • 591 - 597

PubMed ID

  • 2582712

International Standard Serial Number (ISSN)

  • 0009-9236

Digital Object Identifier (DOI)

  • 10.1038/clpt.1989.190


  • eng

Conference Location

  • United States