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Interactions of aspirin with acetaminophen and caffeine in rat stomach: pharmacokinetics of absorption and accumulation in gastric mucosa.

To study the pharmacokinetic interactions between aspirin (250 mg/kg) and simultaneously administered oral acetaminophen (125 mg/kg) or caffeine (50 mg/kg) in male rats, noninterfering GLC assays for these drugs were developed. Acetaminophen and caffeine both retarded the appearance of salicylate in plasma. During the elimination phase, acetaminophen enhanced plasms salicylate levels whereas caffeine did not. Aspirin reduced the plasms levels of both acetaminophen and caffeine during absorption and elimination. Regardless of whether the drugs had been administered separately or in combination, higher concentrations of salicylate, acetaminophen, and caffeine were found in the glandular part of the stomach compared to the nonglandular part (rumen). In both parts, the absorption of acetaminophen increased in the presence of aspirin. Simultaneous administration of aspirin with caffeine did not influence the absorption of either drug in the glandular and ruminal parts. The inhibitory action of acetaminophen and the potentiating action of caffeine on the erosive activity of aspirin are not due to any effects of these drugs on salicylate accumulation in glandular tissue.