ANTIBIOTIC SUBSTANCES 229 



toxicity was Na, Sr, NH4, Ca, K, and Mg. It was concluded that the 

 toxicity of the salts of penicillin is primarily due to the cations used in 

 their preparation. 



Penicillin is not inactivated by saliva, bile, or succus entericus, but is 

 destroyed rapidly by gastric juice, due not to the pepsin but to the HCl 

 in the juice (724, 725). 



Penicillin is slowly absorbed and excreted, usually within one hour, 

 in the urine (725). The degree of its antibacterial action is proportional 

 to its concentration in the serum, maximum effects against hemolytic 

 streptococci being produced by concentrations of 0.019-0. 156 Oxford 

 units in i ml. of serum. The LD50 for an 18-gram mouse was 32 mg. 

 of the sodium salt (422, 424). The cardinal symptoms of toxicity were 

 choking, gasping, and rapid respiration. However, it is relatively non- 

 toxic in doses used for therapeutic purposes (163, 164, S^^, 753). 



Penicillin was thus found to combine the two most desirable quali- 

 ties of a chemotherapeutic agent, namely, a low toxicity to tissue cells 

 and a highly bacteriostatic action against some of the most common and 

 destructive bacteria with which man may become infected. It was pos- 

 sible to maintain a bacteriostatic concentration of penicillin in the blood 

 without causing any toxic symptoms, and to recover a large proportion 

 of the substance from the urine j this recovered penicillin could then 

 be used again. 



Animal Experiments. In animal experiments (699) it was estab- 

 lished that penicillin is an effective chemotherapeutic agent against 

 pneumococci, including sulfonamide-resistant types. In experiments 

 with S. aureus, a survival ratio of 2 : i was obtained in favor of penicillin 

 as compared with sulfathiazole, correction being made for the survival 

 of control mice. Penicillin, when administered subcutaneously, intra- 

 venously, or intraperitoneally, was also found to be effective against 

 hemolytic streptococci (418). Generalized staphylococcal infections 

 were cured by penicillin and local lesions healed during parenteral ad- 

 ministration. The best method for administering penicillin was by the 

 intramuscular route at 3-hour intervals j the blood should contain 

 enough penicillin (15,000 Oxford unit dose) to inhibit the growth of 

 the infecting agent (276, 399, 404). Intraocular infection caused by 

 D. fneumoniae was checked by local treatment with penicillin in solu- 



