Journal of Pharmacokinetics and Biopharmaceutics

, Volume 15, Issue 2, pp 133-143

Time-dependent variations in the organ extraction ratios of acetaminophen in rat

  • Pierre M. BélangerAffiliated withEcole de Pharmacie, Université Laval
  • , Marcel LalandeAffiliated withEcole de Pharmacie, Université Laval
  • , François DoréAffiliated withDépartement de Pharmacologie, Université Laval
  • , Gaston LabrecqueAffiliated withEcole de Pharmacie, Université Laval

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The pharmacokinetics of a single 40mg/kg dose of acetaminophen was investigated at 09h00 and 21h00 in Sprague-Dawley rats synchronized to a 12-h light-dark cycle. Acetaminophen was administered by the intraarterial, intravenous, intraperitoneal, and oral routes in order to determine the contribution of the gastrointestinal tract, liver, and lung to the oral extraction ratio of the drug. A mean oral extraction ratio of 0.46 was obtained at 21h00 as compared to 0.39 at 09h00. The mean extraction ratios of the gastrointestine, liver, and lung were 0.05, 0.41, and 0 at 09h00 and 0.18, 0.24, and 0.13 at 21h00, respectively. These results indicate that the extrahepatic metabolism of acetaminophen is important at 21h00, but is barely detectable at 09h00, whereas the hepatic extraction ratio is higher at 09h00 than at 21h00. Thus, there are temporal variations in the disposition of acetaminophen in the rat.

Key words

Acetaminophen kinetics temporal variations diurnal variations extrahepatic metabolism extraction ratio chronopharmacokinetics