Impact of dilution on the pharmacokinetic behavior of acetaminophen in rabbits after oral administration

✍ Scribed by Jacques O. de Beer; Guido A. Jacobs; Guido Janssens; Mark A. Martens

• Publisher: John Wiley and Sons
• Year: 1985
• Tongue: English
• Weight: 285 KB
• Volume: 74
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600740321

✦ Synopsis

Seven rabbits received two different acetaminophen solutions by gavage in a randomized crossover fashion. In one administration the dose was given in a concentrated small volume of an ethanolglycerol-water mixture (preparation I). In another administration an identical dose was given in a 10-fold water-diluted volume of the same mixture (preparation 11). Three rabbits also received the same dose in a 1 0-fold original mixture volume (preparation Ill). The acetaminophen concentrations were measured by HPLC in plasma samples collected for 3.5 h after gavage. The lag times ranged from 2.5 to 23 min for preparation I and from 2.2 to 29 min for preparation II. The mean peak plasma concentrations (12.38 pg/mL for preparation I and 9.14 pg/mL for preparation II) and the mean time-to-peak concentrations (26.57 min for preparation I and 36.57 min for preparation II) were significantly different. The total area under the plasma concentration curve and the absorption and elimination half-lives did not, however, differ significantly. For the three rabbits receiving the acetaminophen doses in the 1 0-fold ethanol-glycerol-water mixture volumes (preparation Ill), the total area under the plasma concentration curve obviously was increased.