Abstract
In a previous paper 1 it has been shown that theophylline greatly diminishes the toxicity of Mercurin∗ and Salyrgan at the site of intracutaneous injection. The beneficial action of theophylline in enhancing absorption after intramuscular injection has also been demonstrated 2 and it was found 3 that one mole equivalent (3.88% of theophylline monohydrate) produces the maximum effect. Since this and other data 3 are strongly suggestive of compound formation between theophylline and mercurial diuretics of general structure NaOCO-RII-HgOH it seemed advisable to determine the limiting amount of theophylline necessary to prevent local toxicity.
The experimental procedure was the same as that described before 1 and consisted in the intradermal injection into the abdomen of the rabbit of 0.05 cc. of Mercurin and Salyrgan to which varying amounts of theophylline had been added. Each solution was prepared to contain 39 mg. of mercury per cc. (about 0.2 M) and its pH was accurately determined with the glass electrode.
In the accompanying photograph, taken 24 hours after injection, the mole equivalents of theophylline and pH values for each of the 7 solutions are shown adjacent to the corresponding sites of injection. In all 5 rabbits were injected in this way for Mercurin and 3 for Salyrgan. The results for the 2 drugs are very much alike and were found to be so consistent that only one photograph is shown. It will be seen that the local toxicity decreases in proportion to the amount of theophylline present and in the case of the solutions containing 1, 1.25, and 1.5 mole equivalents, so little reaction was produced that it is difficult to locate exactly the sites of injection.
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