ELIMINATION OF CAFFEIN IN NEPHRECTOMIXED RABBITS. 19 



It may be argued that the difference in the amounts of caffein found 

 in the gastrointestinal canal under those conditions may be due to 

 a decreased rate of absorption in nephrectomized rabbits or when 

 renal function is inhibited, but it has been shown by several investi- 

 gators that this is not likely to be the case. Indeed, experimental 

 evidence points the other way. It was shown by Meltzer and Salant 18 

 and later by Loeb and Fleischer 13 that the rate of absorption from 

 the peritoneal cavity is usually faster after the removal of the kidneys. 



The elimination of caffein in nephrectomized rabbits takes place 

 largely in the intestines, but appreciable amounts have also been found 

 in the gastric contents, the amounts recovered from the stomach 

 varying between 3.3 and 5.28 per cent, while in the intestines 4.47 to 

 10.48 per cent of the amounts injected were separated from the intes- 

 tinal contents 22 hours after the administration of caffein. The total 

 amounts of caffein eliminated 22 hours after its administration were 

 8.88 per cent, 7.70 per cent, and 11.78 per cent. By comparing these 

 results with the elimination of caffein by the kidney, stomach, and 

 intestines of normal rabbits we find that the difference is very small. 

 Thus, the total amounts on a diet of oats and carrots 24 hours after 

 injection were 10.21 and 10.9 per cent of the amount of caffein given, 

 or an average of 10.55 per cent, while the average for the three series 

 of nephrectomized rabbits was 9.45 per cent. There is therefore little 

 difference in the amounts eliminated when the kidneys are intact or 

 when they are removed, owing to the stimulation to greater activity 

 of the epithelium of the gastrointestinal can'al, especially that of the 

 intestines. In this connection the fact may also be mentioned that the 

 presence of caffein in the intestines is due entirely to excretion by the 

 intestinal epithelium. This is proved by the following experiments 

 in which the small intestine was ligated at its upper end: 



Rabbit 810. Weight, 1,820 grams. 



May 18, 1912: 11.20 a. m., laparotomy, small intestine tied near the pyloric opening; 

 two ligatures, one above and one below the common bile duct; 12 m., received 360 

 mg caffein, or 200 mg per kilo, showed the usual symptoms of caffein intoxication; 

 3.30 p. m., chloroformed, about 40 cc of urine found in the bladder, but no caffein 

 present, the stomach contents contained 1.15 per cent and the intestinal contents 7.7 

 per cent, or a total of 8.85 per cent caffein. 



Rabbit 811. Weight, 1,600 grams. 



May 18, 1912: 11.40 a. m., same operation as in No. 810, except that there was one 

 ligature below the bile duct and the bile duct itself was ligated; 12 m., received 200 

 mg caffein per kilo, or a total of 320 mg, showed strongly the usual symptoms of caffein 

 intoxication; 1.45 p. m., found dead, about 30 cc urine were found in the bladdder, but 

 there was no caffein present, the stomach contents contained 2.22 per cent and the 

 intestinal contents 4.81 per cent, or a total of 7.03 per cent, caffein. 



It will be observed that the intestine contained about the same 

 amount of caffein as was found in the experiments in which com- 

 munication between stomach and intestines was open. The absence 

 of caffein in the urine is interesting, as it suggests impermeability of 



