ANTIBIOTICS AS CHEMOTHERAPEUTIC AGENTS 293 



employing only pure streptomycin or impure concentrates which do not 

 possess this factor it is possible to eliminate the undesirable side-re- 

 actions. The second kind of toxicity, which results in a fatty meta- 

 morphosis of the liver and kidney of animals, is an inherent property 

 of streptomycin itself. However, this organ pathology has not been 

 observed in man. 



Streptomycin has been administered to man intramuscularly (every 

 3 to 4 hours, a daily total of i to 4 gm.), intravenously (intermittent 

 or continuous, the latter comprising a daily dose of i to 4 gm.), and 

 subcutaneously (100 mg, per i ml., at 6-hour intervals). It has also 

 been given orally (0.5 to 4 gm. per day in 4 doses) and by nebulization 

 into the tracheobronchial tree (25 to 50 mg. per i ml., for a total of 500 

 mg. daily) as well as by intrathecal administration (414). By the intra- 

 venous route a high serum concentration is produced very rapidly, 

 whereas the same level is obtained but more slowly after intramuscular 

 or subcutaneous injection. However, the blood level falls rapidly fol- 

 lowing a single dose and must be maintained by repeated administra- 

 tions. When given orally or by nebulization into the tracheobronchial 

 tree, no appreciable amount of streptomycin is absorbed into the general 

 circulation. 



The intravenous injection of single doses of 200 mg. of streptomycin 

 gives an immediate concentration in the serum of 32 ng per ml. This 

 falls rapidly to 8 Mg at the end of two hours and to i or 2 |jg at the end 

 of twelve hours. Intramuscular injection of the same amount gives a 

 peak serum level of 1 6 Mg at the end of one hour, followed by a slower 

 drop in serum concentration, with detectable amounts after 12 hours. 

 Streptomycin appears quickly in the urine, 20 to 35 per cent being re- 

 covered in 2 hours and 50 to 70 per cent in the 12-hour period after 

 administration of a single dose. The total recovery varies from 1 5 to 

 85 per cent of the daily dose, with an average of 53 per cent. When 

 given parenterally, small amounts of streptomycin appear in the spinal 

 fluid, namely, i to 2 Mg as compared to 25 [ig in the serum. Follow- 

 ing oral administration, very little streptomycin reaches the serum, and 

 only 0.2 to 0.5 per cent is found in the urine; however, there is a high 

 concentration in the feces. 



An intravenous injection of 600 mg. gave 32.8 Mg per ml. of blood 



