PHARMACOLOGY OF ANTIBIOTICS — WELCH 405 



penicillin, injected intramuscularly, is not stored in the body but is 

 quickly excreted as penicillin or penicillin-decomposition products. 



Early clinical trials with oral therapy were for the most part dis- 

 appointing, and it was felt that this was due to inactivation of the 

 drug by gastric secretions. During recent years, several investigators 

 have shown that the oral route is effective for the treatment of many 

 infections, provided sufficiently large doses are administered at proper 

 midmeal periods. It is generally accepted that approximately five 

 times as much penicillin is required orally as intramuscularly to obtain 

 comparable plasma concentrations of the drug. These large doses 

 are necessary because of the inactivating effect of gastric secretions 

 and food, incomplete absorption, and inactivation by penicillinase- 

 producing bacteria in the intestinal tract. 



Penicillin may be administered by inhalation as an aerosol of finely 

 micronized dust and by instillation in solution into the pleural, peri- 

 cardial, peritoneal, or synovial spaces. By these methods of adminis- 

 tration, a local or topical effect of the drug is obtained and although 

 absorption may occur, it is erratic and unreliable where systemic 

 therapy is needed. Soluble tablets of pencillin (containing nothing 

 but the drug) are available for sublingual use. Satisfactory absorp- 

 tion by this route has been reported and this mode of administration 

 may have a place in the treatment of patients who have difficulty in 

 swallowing the larger penicillin tablets. 



Diffusion of penicillin from the circulation into the tissues depends 

 on the plasma concentrations, and the diffusion into the tissues will 

 proceed as long as the concentration of diffusible penicillin in the 

 plasma exceeds that in the tissues. The drug diffuses readily from 

 maternal to fetal blood and into the abdominal cavity. Some diffu- 

 sion also occurs into the pleural, pericardial, and synovial fluids, and 

 bile. Very little of the drug penetrates into abscess cavities, brain 

 and nerve tissues, bone, chambers of the eye, nor does it appear in any 

 appreciable concentration in sweat, saliva, tears, or milk. Unless 

 large doses are administered, very little diffusion into the cerebro- 

 spinal fluid will occur except where the meninges are inflamed. 



As indicated above, after penicillin is absorbed most of it is rather 

 rapidly excreted in the urine. The renal clearance of crystalline 

 penicillin G approximates the total renal plasma flow. It is about 

 four or five times greater than the renal clearance of inulin or sodium 

 thiosulfate. As a matter of fact, the normal renal clearance of peni- 

 cillin so closely approximates the renal plasma flow that it has been 

 suggested as a possible substitute for para-aminohippuric acid or 

 diodrast as a test for renal plasma flow and renal function. The solu- 

 ble salts of penicillin are excreted in the greatest amounts during the 

 the first hour, but diminishing quantities may be found for several 

 hours thereafter. 



