1. The quantitative determination of Cinchophen and Tolysin in the intestinal contents met with considerable difficulties, inasmuch as the excreta contain large quantities of fats and higher fatty acids. The separation of Cinchophen has been done by extraction with alcohol and by precipitation of the soaps with magnesium-sulphate. In the filtrate of the magnesium-soaps the separation of Cinchophen then has been effected by addition of coppersulphate. The estimation of Tolysin must be preceded by the saponification of the alcoholic extract by alcoholic potash. Then the p-Methylcinchophen resulting from Tolysin may be estimated according to the same principle.
2. Certain sources of error in this method have been overcome by using a petroleum-benzine-cadmiumchloride-method. This improved method is based on the fact, that free Cinchophen and Methylcinchophen are insoluble in benzine and that in alcoholic solution these acids are thrown down quantitatively by cadmium chloride. The compounds separate in a crystalline form as spherules, consisting of concentrical clusters of fine needles.
3. By the magnesium-sulphate-method it has been established, that dogs, having received Cinchophen (2.5 to 7.5 grams) with their food, absorbed 50 to 96 per cent, average 69 per cent (13 experiments).Tolysin (2 to 12 grams) has been found to be absorbed at the ratio of 37 to 98 per cent average 68 per cent (13 experiments). The absorption of Cinchophen in rabbits (2.5 to 6.0 grams) had been between 84 to 100 per cent, average 95 per cent (10 experiments). The absorption of Tolysin in rabbits (4.0 to 5.0 grams) has been found to be about 89 to 100 per cent, average 92 per cent (7 experiments)—Cinchophenanhydride, a substance very scantily soluble in lipoid solvents, had been adsorbed very poorly (0.19 per cent).
4. By the cadmiumchloride-method the absorption of Cinchophen (9.3 and 6.3 grams) has been foun—a quantitative one in 2 dogs. The absorption of Tolysin in dogs (12 to 30 grams) has been found varying between 64 to 98 per cent, average 85 per cent in 8 experiments. Three experiments on human beings, having received 5.5 to 6.6 grams of Tolysin, have shown, that the absorption was practically quantitative (98 to 100 per cent). There is therefore no reason to believe, that the absorption of therapeutic doses of Tolysin is a poor one.
5. From the biochemical point of view it is interesting to note, that Tolysin, as a paradigma of an aromatic ester, insoluble in water and easily soluble in lipoid solvents, does not seem to undergo saponification to a great extent before its adsorption from the intestinal tract. It therefore seems probable, that Tolysin is absorbed by the intestinal mucosa, without having undergone saponification before and we may suppose, that the complicated physiochemical medium, consisting of fats, higher fatty acids, lecithin, cholesterol and biliary acids, present in the intestinal contents, acts as its solvent. The same may apply to the absorption of many other aromatic esters, insoluble in water and readily soluble in lipoid solvents.