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

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 ethanol-glycerol-water mixture (preparation I). In another administration an identical dose was given in a 10-fold water-diluted volume of the same mixture (preparation II). Three rabbits also received the same dose in a 10-fold original mixture volume (preparation III). 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 micrograms/mL for preparation I and 9.14 micrograms/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 10-fold ethanol-glycerol-water mixture volumes (preparation III), the total area under the plasma concentration curve obviously was increased