HISTORICAL REVIE^ 7 OF THE LITERATURE. 7 



remarked that paraldehyde was given simultaneously when caffein 

 was administered. Whether or not this had any effect on the elimi- 

 nation of caffein does not appear in the protocols to Rost's experi- 

 ments, as no controls were made. The diet of these animals con- 

 sisted of carrots entirely, or sometimes of carrots and bread. It 

 would seem, therefore, that by far the greatest part was eliminated 

 in the case of the rabbit during the first twenty-four hours ; moderate 

 amounts during the second twenty-four hours and only very small 

 quantities during the next day. 



Experiments on dogs show that these animals eliminated much 

 smaller amounts of caffein than did rabbits. After the administra- 

 tion of 0.1 to 0.4 gram by mouth, 1.1 to 8.1 per cent of caffein was 

 found in the urine of five days. Only one experiment was made by 

 subcutaneous injection, after which 1.2 per cent of caffein was found 

 in the urine of three days. 



The amounts of caffein in the urine of cats and of man after the 

 administration of moderately large quantities were found to be even 

 much smaller than in that of dogs. Thus traces only were detected 

 by Rost in the five days' urine of two cats, while 2.4 per cent of caffein 

 was found in the case of another cat. Similar results were obtained 

 for man. After ingesting 0.25 gram caffein, traces only were found 

 n the urine collected in eighteen to twenty-four hours. When 0.5 

 gram caffein was ingested 0.45 per cent was recovered in seventeen 

 hours' urine, and 0.6 per cent in the urine of twenty-four hours. 



It appears, therefore, from the findings of Rost that the rabbit 

 eliminated the largest amount of caffein unchanged, while in the cat 

 and in man only minimal quantities found their way into the urine. 

 Although the amounts of caffein reported by Rost undoubtedly 

 represent all of the alkaloid eliminated by the kidney, as in some 

 instances the urine of fixe days was examined, there is no evidence 

 of the purity of the product obtained, as neither the melting point 

 nor other tests, chemical or physiological, were made to identify the 

 substance. Rost (15) assumed that the repeated extraction with 

 alcohol, chloroform, and sodium benzoate is bound to extract caffein 

 only. 



Bongers (4) studied the elimination of caffein into the stomach; 

 after the subcutaneous injection of 1.0 gram of caffein sodium salicylate 

 into a dog, the examination of the contents of the stomach proved 

 negative. When the dose was increased to 1.5 grams and adminis- 

 tered the same way the contents of the stomach obtained half an 

 hour later gave a distinct reaction for caffein by the method of 

 Schwarzenbach. Alcohol, benzol, and chloroform were used for the 

 extraction of caffein. 



Later Martin Kriiger (8) reported experiments on two dogs which 

 received 50.5 grams of caffein in nearly three weeks. The urine of the 



