PHARMACOLOGY OF ANTIBIOTICS — WELCH 415 



celerated. There was no associated pruritis. These symptoms per- 

 sisted for about 30 minutes and then subsided spontaneously. The 

 same syndrome occurred after the last dose of drug was given. 

 Stomatitis may be a possible side reaction to chloramphenicol and 

 some looseness of stools or diarrhea may occur. In the treatment of 

 syphilis a mild Jarisch-Herxheimer reaction has been noted. This 

 reaction is perhaps less frequent in patients treated with chloram- 

 phenicol than those treated with penicillin. In general, fewer cases 

 of loose stools and diarrhea are reported with chloramphenicol than 

 with either aureomycin or terramycin. An explanation of this, in 

 part at least, may be the rapid absorption of the chloramphenicol from 

 the gut and the rapid inactivation of that remaining in the intestine. 

 In addition, little antibacterial effect is obtained on the intestinal flora 

 in contrast to the rather profound antimicrobic effect of terramycin 

 and aureomycin on these organisms. Yeasts are frequently found to 

 make up a great proportion of the intestinal flora following extended 

 treatment with either terramycin or aureomycin, while chlorampheni- 

 col has little or no such effect. 



Proliferating epithelial cells and fibroblasts and cells from explants 

 of embryonal brain tissue are retarded in their growth in vitro by 

 concentrations of chloramphenicol of 10 fxg. per ml. This, of course, 

 is in the range obtained with certain dosage regimens of this drug. 

 The cells are completely inhibited in their growth by concentrations 

 of 1,000 fig. per ml. The latter amount is well beyond the blood 

 concentration of the drug obtained in clinical use. In view of the 

 large amounts of chloramphenicol that have been used clinically in 

 man, it does not appear that its effect on the growth of proliferating 

 cells is of clinical significance. 



Absorption and excretion. — Chloramphenicol is very rapidly ab- 

 sorbed from the intestinal tract in man. It is metabolized readily and 

 excreted by way of the kidneys. Present evidence indicates that 

 approximately 90 percent of the administered dose may be accounted 

 for in the urine in a period of 24 hours, although relatively low con- 

 centrations of active chloramphenicol are found. Probably less than 

 10 percent of the administered dose is excreted unchanged, while a 

 great bulk of the drug is excreted in the form of an inactive nitro 

 compound. 



Although lower concentrations of active chloramphenicol are dem- 

 onstrated in the urine following the oral use of this drug, the blood 

 concentrations obtained with chloramphenicol are somewhat higher 

 than those obtained following comparable oral doses of terramycin and 

 aureomycin. The concentration of chloramphenicol in the blood drops 

 off rapidly so that by the sixth hour its concentration is somewhat 

 lower than that obtained with similar doses of either terramycin or 



