PHARMACOLOGY OF ANTIBIOTICS — WELCH 417 



excretion of these drugs following oral administration. Both drugs 

 are readily absorbed from the gastrointestinal tract and are readily de- 

 monstrable in the blood and urine. In addition, appreciable amounts 

 are excreted in the feces and thereby alter the intestinal flora of the 

 patient. As with aureomycin, complete disappearance of terramycin 

 from the blood may occur as late as the twenty-fourth to thirtieth 

 hour after single doses. There is, however, a definite diminution in 

 the amount of terramycin in the blood 6 to 8 hours after single doses of 

 0.5 to 2.0 grams. In contrast to aureomycin, which is not very stable 

 in solution, terramycin is quite stable in the presence of serum, urine, 

 and other body fluids. Terramycin does not readily traverse the 

 blood brain barrier as aureomycin does although in cases where the 

 meninges are inflamed, terramycin has been demonstrated in the cere- 

 brospinal fluid. Terramycin diffuses readily into the pleural fluid 

 and passes through the placenta and is present in the fetal circulation. 

 The drug is also excreted readily in the bile. The serum concentra- 

 tions of terramycin after oral administration are relatively high and 

 prolonged. As the dose is increased from 0.5 to 2.0 grams there is a 

 tendency for the serum concentration to increase correspondingly at 

 any given time. However, the increase in serum concentrations of 

 this drug following single oral doses of from 1 to 2 grams is not quite 

 as great as one would expect, and furthermore the serum content of 

 terramycin is not significantly increased by increasing the size of a 

 single dose from 1 to 3 grams. It appears that only a certain amount 

 of terramycin is absorbed from the circulation regardless of the size 

 of the oral dose. Blood concentrations of terramycin can be main- 

 tained at a relatively high level by oral administration every 6 hours. 

 Following oral administration of 0.25 gram, 0.5 gram, and 1.0 gram 

 given at 6-hour intervals for a period of 24 hours, serum concentrations 

 rise sharply with increased dosage. 



Urinary excretion of terramycin is relatively high following both 

 single and multiple doses. Indeed, considerably more terramycin 

 is found in the urine than aureomycin after similar doses. The dif- 

 ferences in recovery of terramycin and aureomycin in the urine fol- 

 lowing the same dose do not appear to be fully explained on the 

 basis of the instability of aureomycin in urine. 



SUMMARY 



Pharmacologically, the clinically useful antibiotics are a unique 

 group of drugs. Penicillin is nearly nontoxic but may cause annoying 

 allergic manifestations especially when given topically. Both strep- 

 tomycin and dihydrostreptomycin are essentially nontoxic when given 

 over short periods of time, although repeated dermal exposure to 

 either drug may give rise to allergic phenomena, and both drugs may 



