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Effect of ethanol on the intramuscular absorption of water-soluble drugs in the rat.

The effect of ethanol on the intramuscular absorption of water-soluble drugs from the rat thigh muscle was investigated. The presence of ethanol caused a pronounced decrease in the absorption rate of drugs, and the reduction was reflected by the decrease in plasma concentrations. It was also found that the absorption rate of drugs from the site of injection depends mainly on the concentration rather than the absolute amount of ethanol. A direct relationship between the relative viscosity of the injectable solution and the inhibitory absorption was demonstrated at lower concentrations of ethanol, but not at higher concentration. This shows that the inhibitory absorption effect of ethanol cannot be adequately explained by simple physicochemical factors, such as viscosity, but the existence of other factors must be acting. A constant intravenous infusion of ethanol showed no effect on the intramuscular absorption of drug. Furthermore, ethanol did not significantly change the permeability of the isolated mesentery to drug molecules. On the other hand, the connective tissue permeability was significantly decreased by the presence of ethanol and had a good correlation to the inhibitory effect of ethanol on the intramuscular absorption of drugs. From these observations, it can be concluded that the mechanism of the inhibitory effect of ethanol is mainly due to its influence on the extracellular spaces and the connective tissues permeability.