EXPEKIMENTS ON RABBITS. 9 



purpose the appearance of the residue to the trained eye, together 

 with its complete sublimation, was considered sufficient for its 

 identification and the proof of its purity.. The melting point was 

 determined in a good many cases but not in all, while sublimation 

 was tried in every case. 



The elimination of cafTein was studied in rabbits, guinea pigs, in 

 cats and dogs, the -object of this investigation being the determina- 

 tion of the amount of cafFein excreted as compared with the quan- 

 tity introduced, as well as to gain some information concerning the 

 rate of elimination, with due regard to possible factors which might 

 influence this process. The mode of administration, the size of the 

 dose, and diet were considered possible factors which may influence the 

 rate of elimination. Its elimination in the urine was studied chiefly, 

 but the contents of the various sections of the gastrointestinal 

 canal were also examined for cafTein after the drug was given. 



Two, or more frequently three, animals were used for every experi- 

 ment, excepting those on dogs, and the urine was combined and exam- 

 ined for cafTein. The same procedure was employed in the case of the 

 contents of the digestive tract or of the bile. This was done in order 

 to make the detection of small quantities possible and to reduce 

 individual variations by obtaining an average of several subjects in 

 each case. 



EXPERIMENTS ON RABBITS. 

 General Discussion. 



The elimination of cafTein was studied in animals on different diets, 

 some receiving oats and some carrots, while others were given hay 

 exclusively. The doses administered varied between 50 and 150 mg 

 per kilo, the subcutaneous method being employed in all the experi- 

 ments except one in which the drug was given by mouth. 



It was found that considerable amounts of cafTein were eliminated 

 in the urine of the rabbit and that it varied appreciably, in different 

 subjects, the difference being especially marked on oat diet. More- 

 over, the average amounts recovered strongly suggest that the per- 

 centage eliminated is distinctly smaller with oats than with carrots, 

 the elimination on a diet of hay being intermediate in amount. 

 After the subcutaneous injection of 150 mg per kilo the amounts 

 recovered at the end of twenty-two to twenty-four hours in one series 

 of rabbits (Series I) averaged 9.6 per cent when fed oats and 11.62 per 

 cent when fed carrots. In another series of experiments (Series II) 

 the results obtained were reversed, i. e., more cafTein was eliminated 

 during approximately the same time by animals that received oats 

 than by those that were fed carrots, the percentage in the former being 

 12, while in the latter it was 11.23. This seemed to be exceptional, 

 37880°— Bull. 157—12 2 



