PHARMACOLOGY OF ANTIBIOTICS — WELCH 413 



Although aureomycin is used in large part orally, the intramuscular 

 and intravenous routes of administration have been explored. Intra- 

 muscularly, aureomycin causes considerable irritation and is extremely 

 painful. There is no preparation commercially available at this time 

 for intramuscular use. There is, however, an intravenous dosage 

 form. This method of parenteral administration is very valuable, 

 perhaps essential in certain types of cases. In comatose patients and 

 those unable to swallow, intravenous aureomycin has been used with 

 considerable success. Unfortunately, even when used with the special 

 diluents, glycine and leucine, phlebitis occurs in approximately 10 

 percent of patients so treated. This reaction subsides promptly with- 

 out serious residual effect as soon as this form of medication is stopped. 

 Both nausea and vomiting have been reported following the intraven- 

 ous use of aureomycin. 



Aureomycin retards proliferation of fibroblasts, epithelial cells, and 

 cells from explants of embryonal brain tissue at levels approaching 

 those obtained in patients under treatment with this drug. At con- 

 centrations of 1,000 /xg. per ml., inhibition of growth of these cells has 

 been obtained. These toxic manifestations of aureomycin appear to 

 be of little clinical significance. 



Aureomycin, like all drugs, will sensitize some individuals. The 

 evidence so far indicates that the incidence of patients who become 

 sensitive to the drug is extremely low. Furthermore, it is rarely nec- 

 essary to withdraw the drug from those patients who develop re- 

 actions to it. 



In considering the toxicity of aureomycin, one should not forget its 

 relative toxicity as compared to that of penicillin which for all prac- 

 tical purposes is considered atoxic. The average oral dose of crystal- 

 line penicillin G is 100,000 units (0.06 gram) every three hours. A 

 million units of penicillin is 0.6 gram, yet doses of aureomycin as high 

 as 30 grams orally have been used without serious toxic reactions. One 

 must conclude that we have in aureomycin a drug practically free from 

 toxicity. 



Absorption and excretion. — Aureomycin is readily absorbed from 

 the intestinal tract when administered orally in capsule form. Fol- 

 lowing absorption it diffuses into all body fluids and tissues. In 

 single doses of from 0.75 to 1.0 gram, therapeutic serum concentra- 

 tions are obtained quite rapidly and these are maintained for rela- 

 tively long periods of time. These serum concentrations are main- 

 tained at therapeutic levels for 6 to 8 hours and complete disappear- 

 ance from the circulation is not observed for from 24 to 30 hours. 

 When doses of 0.5 gram to 1.0 gram are administered to patients every 

 6 to 8 hours, the serum concentration of the drug is maintained at 

 from 2 to 4 /*g. per ml., although the concentrations in some patients 



