406 ANNUAL REPORT SMITHSONIAN INSTITUTION, 1952 



Because penicillin is absorbed and excreted rapidly, numerous 

 attempts were made to develop pharmaceutical forms of the so-called 

 "repository types" which would allow a slow and more or less con- 

 stant release of penicillin into the general circulation from a tissue 

 depot. The first of these was a suspension of penicillin in peanut oil 

 and wax. With the development of procaine penicillin, penicillin in 

 oil and wax became less and less popular until at the present time 

 practically none is available commercially. Procaine penicillin either 

 in oil or in aqueous suspension is slowly absorbed from a tissue depot 

 because of its insolubility. This drug has a solubility of only 0.67 

 percent. Further prolongation of blood concentrations of procaine 

 penicillin in oil is obtained by the addition of 2 percent aluminum 

 monostearate. The latter drug has been used in tremendous amounts 

 during the past few years. Obviously the addition of peanut oil, 

 sesame oil, beeswax, and other substances to penicillin increases the 

 possibilities of sensitization. The occasional side reactions obtained 

 with the so-called repository forms of penicillin, however, have not 

 mitigated against their use. 



In attempts to prolong the activity of penicillin in the body, agents 

 that compete with penicillin for the same renal excretory mechanism 

 have been proposed. These agents, para-aminophippuric acid, dio- 

 drast, and carinamide, act by retarding the excretion of penicillin, thus 

 prolonging its presence in the blood. Eecently a new, relatively 

 nontoxic compound, p-(di-N-propylsulfamyl) -benzoic acid 2 has been 

 shown to retard the excretion of penicillin with a daily dose of 2.0 

 grams (0.5 gram every 6 hours) to the same extent as a daily dose 

 of 24 grams of carinamide (3 grams every 3 hours). This drug also 

 delays the excretion of para-aminosalicylic acid, and because of this is 

 under study in combination with para-aminosalicylic acid in the treat- 

 ment of tuberculosis. 



STREPTOMYCIN AND DIHYDROSTREPTOMYCIN 



The speed with which streptomycin was demonstrated to be an effec- 

 tive weapon in the fight against infectious diseases was in part due to 

 the great need for an agent active against the gram-negative organisms 

 and the mycobacteria. Within a year of the announcement of the 

 discovery of this drug, its in vivo activity was established and in spite 

 of extremely short supplies, it had been shown clinically to be a safe 

 and effective chemotherapeutic agent. It is the first and only drug 

 of proven value that phthisiologists have had in the treatment of 

 tuberculosis. Unfortunately, it is not the answer to definitive treat- 

 ment of this disease although there is no question but that it is a 

 most valuable adjunct to other forms of therapy. 



1 "Benemid" — trademark. 



