MUTAGENS OF POTENTIAL SIGNIFICANCE 205 



Other experiments have shown that the maximum level is reached 

 even sooner. The efficiency of absorption of caffeine can be estimated 

 directly by comparing plasma levels after intravenous and oral ad- 

 ministration, by direct analysis of the tissues of experimental animals, 

 or by applying to the plasma levels a knowledge of the total aqueous 

 volume in which the drug is distributed. All these methods have been 

 applied, and they all agree. 



Axelrod and Reichenthal have shown that in human subjects the 

 plasma levels at one hour are identical, whether the drug has been given 

 orally or intravenously. They also demonstrated in the dog (Table 5) 



TABLE 5 



Distribution of caffeine in dog. 



84 mg/kg i.v. was given 3 liours before animal was killed. 

 Data of Axelrod and Reichenthal (3). 



that after 3 hours equilibration, after an intravenous dose, all the 

 tissues and the plasma have about the same caffeine concentration, and 

 this concentration is very nearly the same, per kg., as the total ad- 

 ministered dose. Thus caffeine equilibrates completely in the body 

 water compartments of all tissues. There is certainly no reason to 

 think the gonads would behave differently, although they were not 

 examined in this study. Finally, analyzing Figure 28A, if we assume 

 distribution into all body water of man, as in the dog, and take 75 

 kg. as the approximate weight of our subjects, 62 per cent of body 

 weight as total body water, 5 mg/1 the level after 300 mg ingested, we 

 find more than three-fourths of the administered caffeine was absorbed, 

 and there are some reasons to think this may be an underestimate. We 



