Abstract-In our studies with drug combinations, we searched for mixtures which would enhance the effectiveness of the related active substances. Ethenzamide was found to possess a specific suppressive effect on the gastric damage induced by aspirin.Such effect could not be demonstrated in analgesic agents such as salicylamide, bucetin, acetaminophen and phenacetin. The combination of aspirin with ethenzamide had a potentiating effect on analgesic activity and reduced motor incoordination and loss of righting reflex.We calculated the safety margins of various ratios of combinations and concluded that the best was aspirin and ethenzamide at a ratio of 2:3.The general principle in considering drug combinations containing two or more in gredients is to evaluate not only the enhancement of the main effect and/or the magnification of the pharmacological spectrum of each ingredient but also the usefulness of the combi nation from the standpoint of total effect. We further propose that this principle should include increasing the safety margin so that drug combinations have greater safety margins than do the ingredients as single entities (1, 2, 3).Aspirin although in wide use does induce gastrointestinal damage. As such an untoward effect often limits extensive clinical application, we searched for a compound which would enhance the usefulness of aspirin when used in combination with other agents. MATERIALS AND METHODSAspirin, ethenzamide, salicylamide, bucetin, acetaminophen, phenacetin and five mixtures of aspirin and ethenzamide were used. Such were prepared in accordance with the ratios shown in Table 1. All orally administered test agents were suspended in I gum arabic solution. SLC-ddY male mice weighing 24±2 g were used.For each dose studied, a group of either 5 or 10 mice was employed in each experiment. Gastric damages induced by aspirin combined with various mild analgesicsThe method of Fiikawa et al (4) was followed. The mice were deprived of solid food but allowed free access to drinking water for 18 hr prior to experiments. The animals were sacrificed by cervical dislocation 4 hr after administration of drugs. The stomachs were rapidly exposed and fixed with 5 % formalin for 3 min. Gastric damages were observed under a stereoscopic microscope, and the length of erosive lesions (L.E.) was measured.The cumulative frequency was obtained from frequency distribution of 10 mice by L.E.

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