PHARMACOLOGY OF ANTIBIOTICS — WELCH 409 



tion has been used, it is no longer recommended, not only because of 

 inconvenience to the patient but also because constant high blood 

 concentrations are unnecessary. This is particularly true in the 

 treatment of tuberculosis where prolonged high concentrations of the 

 drug are not essential and in addition increase the possibility of 

 neurotoxic reactions. The rapid disappearance of streptomycin from 

 the blood can be accounted for by its early appearance in the urine. 

 Following oral administration of the drug in animals relatively small 

 amounts are found in the blood. This lack of absorption of strepto- 

 mycin from the gastrointestinal tract is responsible for the low blood 

 concentrations and is consistent with the large amount of drug re- 

 covered in the feces. In general, these results are similar to those 

 found following oral use of streptomycin in man. The drug may be 

 concentrated and excreted in the bile. It passes the placental barrier 

 and is readily available to the fetal circulation. 



Streptomycin cannot be demonstrated in the blood serum of patients 

 following the administration of 0.5 gram per day by nebulization or 

 by mouth and, furthermore, urinary excretion of streptomycin under 

 these conditions is negligible. Injections of from 50,000 to 100,000 fxg. 

 per day intrathecally for meningitis show from 6 to 50 //.g. per ml. in 

 the spinal fluid 12 hours later. No significant amounts of strepto- 

 mycin appear in the spinal fluid following intramuscular or subcu- 

 taneous injections of from 50,000 to 200,000 fig. In patients with 

 tuberculous meningitis receiving streptomycin by continuous subcu- 

 taneous infusion for over 48 hours, streptomycin may be demonstrated 

 in the spinal fluid in amounts varying from 4 to 18.5 jig. per ml. It 

 would appear that the presence of an inflammatory reaction in the 

 meninges increases the possibility of diffusion of streptomycin into 

 the spinal fluid. In man, the serum concentration obtained within 

 1 hour after intramuscular injection of streptomycin approximates 

 that obtained by intravenous injection of the same dose indicating a 

 rapid absorption from the muscle. Streptomycin is absorbed more 

 slowly following intramuscular or subcutaneous injection than is 

 penicillin and similarly is excreted at a slower rate. Blood concen- 

 trations may be maintained for approximately 12 hours following 

 the injection of 0.5 gram of streptomycin as the sulfate. 



Most of the streptomycin injected parenterally is excreted through 

 the kidneys and although rather broad variations in percent recovery 

 of streptomycin in the urine of man have been reported, it appears 

 that where normal kidney function is involved, between 50 and 60 

 percent of the streptomycin administered parenterally is excreted in 

 the urine within a 24-hour period. Excretion of the drug is most 

 rapid in the first 4 hours while the greater part of the antibiotic is 

 excreted in the urine within the first 12 hours. Obviously in the 



