10 THE ELIMINATION OF CAFFEIN. 



however, as in other experiments (Series III) the total amounts of 

 caffein recovered were 13.41 and 6.63 per cent with animals fed respec- 

 tively on carrots and oats. The difference was much more striking 

 with smaller doses (Series IV and V). After the subcutaneous admin- 

 istration of 50 mg per kilo from 1.72 to 5.33 per cent of caffein was 

 obtained from the urine of rabbits fed on oats, while those fed on 

 carrots eliminated in the urine 7.18 and 11.38 per cent. 



A difference in the amounts eliminated was also observed when 

 caffein was given by mouth. The amounts recovered from the urine 

 were 9.5 per cent when the diet consisted of oats and 14 per cent 

 when carrots were fed (Series VI). Diuresis suggests itself as a 

 possible cause of the larger amounts eliminated on a carrot diet. 

 The following experiments would seem to furnish some support for 

 this view. In Series I rabbits fed on oats passed 250 cc of urine 

 In 'three hours and eliminated 3.8 per cent of the caffein injected. 

 Parallel experiments on animals receiving carrots showed an elimina- 

 tion of 4.75 per cent of the caffein administered; the amount of urine 

 passed was 360 cc in three hours. 



Two series of experiments in which hay was fed (Series VIII and 

 IX) also indicated that diuresis favors better elimination of caffein, 

 as the amount recovered in one series was 6 per cent and in another 

 it was 4.8 per cent, the quantity of urine eliminated during the ex- 

 perimental period being 570 cc in the former and 345 cc in the 

 latter case. Diuresis, however, is in all probability only one of the 

 factors concerned in the elimination of caffein, as this does not always 

 account for the differences in the amounts recovered, and it is con- 

 ceivable that diet may likewise play an important part. Since the 

 amount of caffein eliminated unchanged is an index of its decompo- 

 sition in the body it follows that the greater the quantity obtained 

 in the various channels of excretion the less the demethylation in 

 the body. It is quite probable, therefore, that demethylation is 

 greatest when hay is fed, less when oats, and least when carrots 

 form the exclusive diet. In the studies on toxicity already reported 

 (Bulletin 148) it was found, however, that the resistance to caffein 

 was the same whether oats or carrots were fed. This may be ac- 

 counted for by the fact that the toxic dose of caffein is quite large and 

 varies a good deal for individuals of the same species, so that toxicity 

 may be masked by these factors. 



In the experiments which were made on the rate of elimination 

 it was found that caffein disappeared from the urine within about 

 forty-eight hours after its administration. A very small amount 

 was found later in some experiments, but in most of them the urine 

 obtained on the third day after the administration of caffein failed 

 to show the presence of the alkaloid. The amounts found in the 

 urine in the second twenty-four hours were usually small, seldom 



