Acetaminophen-diphenhydramine interaction in rabbits

International Journal of Pharmaceutics (Impact Factor: 3.65). 06/1981; 8(4):277-284. DOI: 10.1016/0378-5173(81)90067-3


Acetaminophen-diphenhydramine interaction was investigated by oral administration of acetaminophen to rabbits, alone or in combination with diphenhydramine. Blood samples were collected before and 0.25. 0.5, 0.75, 1.0, 2.0, 3.0, 4.0, 5, 0 and 6.0 h after acetaminophen administration. Assays of acetaminophen in plasma samples were carried out using a HPLC method. Diphenhydramine significantly reduced the maximum plasma concentration (Cmax) of acetaminophen. Diphenhydramine, however, had little effect on the time taken to reach the maximum plasma concentration (Tmax), the area under the plasma concentration-time curve (AUC∞0) and the elimination half-life (t) of acetaminophen. Gastric emptying experiment was performed by injecting into the rabbit stomach phenol-red containing solution with and without diphenhydramine. The gastric content recovered at 0.5 h was analyzed for phenol-red remaining to determine the rate of gastric emptying. Diphenhydramine significantly increased the weight percentage of phenol-red remaining in the rabbit stomach 0.5 h post-injection. It was concluded that diphenhydramine affected the rate but not the extent of acetaminophen absorption by delaying the gastric emptying.

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