PHARMACOLOGY OF ANTIBIOTICS — WELCH 411 



fleeted in the blood NPN, in the urinary albumin, and in low phenol- 

 sulfonphthalein excretion. Abnormal urinary changes are observed 

 after the eighth or tenth injection with daily doses of 40,000 to 80,000 

 units and after the second injection of a single daily dose of 100,000 

 units for 2 days. Evidences of liver damage have not been reported 

 and no significant effects have been noted on erythrocytes or white 

 blood cells. 



Absorption and excretion. — Bacitracin is absorbed readily follow- 

 ing intramuscular injection but disappears from the blood less rapid- 

 ly than does penicillin. Intramuscular injection of bacitracin in man 

 produces higher and more prolonged blood concentrations than those 

 observed after penicillin administration. The differences in the blood 

 concentrations of penicillin and bacitracin have been shown to be due 

 to their different rates of urinary excretion. In contrast to the mech- 

 anism of excretion for penicillin, bacitracin is cleared by the kid- 

 neys at a rate approximating that of glomerular filtration. 



Following parenteral injection of bacitracin in animals, the drug 

 is found in the urine, kidney, blood, bile, lung, bone marrow, skin, 

 heart, muscle, skeletal muscle, liver, spleen, cerebrospinal fluid, and 

 brain. In man, bacitracin readily diffuses into the pleural and per- 

 itoneal cavities. In general, following large intramuscular injec- 

 tions of this drug in man in the absence of inflamed meninges, baci- 

 tracin is not usually recovered in the cerebrospinal fluid. 



When 50,000 units or about one-half of the maximum daily dose is 

 administered intramuscularly, the peak concentration of the drug in 

 the blood develops by the fourth hour, after which the concentration 

 gradually declines. Individual variation in blood concentrations may 

 be quite marked following intramuscular use. Blood concentrations 

 following injection of 50,000 units may vary from 0.03 unit per ml. to 

 0.8 unit per ml. 



The oral administration of bacitracin does not ordinarily result in 

 measurable blood concentrations, the greater portion of the total dose 

 being recoverable in the feces. Following unusually large oral doses 

 or prolonged oral administration, however, a trace of activity may be 

 observed in the blood and measurable amounts found in the urine, in- 

 dicating that some absorption has occurred. 



Bacitracin, after parenteral administration, is excreted mainly by 

 way of the urine. Wide discrepancies exist concerning its excretion. 

 In one experiment 10 to 30 percent of the injected dose was excreted 

 in the urine within 24 hours and this suggested that the greater por- 

 tion was either retained in the body or inactivated. Others have 

 found that practically 100 percent of the dose administered could be 

 accounted for by urinary excretion within 8 hours. The fact that in 

 one case much smaller doses were used may account for this discrep- 



