An Experimental Study on the Influence of Different Vehicles on the Generalized and Topical Effect of Penicillin G *

As a rule, the effect of different vehicles on the activity of penicillin has been studied by the determination of the penicillin concentration in plasma and serum. From these data, the necessary deductions as to the clinical usefulness and methods of administration were made. Even if vehicles other than water and saline were used in experimental investigations2 6 no comparison was made with the effects of aqueous solutions. In the course of our studies on the mechanism of activity of penicillin4' ' it was felt that the methods employed in these studies could probably be applied to an investigation of the influence of different vehicles. Comparative experiments were, therefore, carried out in which the effect of penicillin G in various carriers was evaluated in generalized and localized streptococcal infections. The systemic as well as the topical activity was investigated using the arrangement of the therapeutic as well as the prophylactic administration of the drug. The results are presented in this paper. Materials and methods White mice 18 to 20 gm. in weight were used in all the experiments. A. Systemic infection: (1) Therapeutic experiments: Mice were infected intraperitoneally with 0.5 ml. of a 10-5 dilution of a 22-hour serum broth culture of Streptococcus hemolyticus #4 (Group A, type 3). This dose corresponds to 1000 MLD. The treatment consisted of a total dose of 36 mcg., 75 mcg., 150 mcg., 300 mcg., or 600 mcg. crystalline penicillin G (Roche) dissolved in saline or suspended in oil. The various dosages were given in two treatments, one immediately following infection and the other four hours later. (2) Prophylactic experiment: Mice were given a single subcutaneous injection of 7500 mcg., 15,000 mcg., or 30,000 mcg. of crystalline sodium penicillin G dissolved in saline or gum, or suspended in oil or oil plus beeswax (Romansky mixture). Two to four hours after treatment, the animals were infected with 0.5 ml. of a 10-5 dilution of a 22-hour serum broth culture of Streptococcus hemoI ticus #4 (Group A, type 3) intraperitoneally. Local infection: Two-tenths milliliter of a 1: 15 dilution of a 22-hour serum broth culture of Streptococcus hemolyticus B (Group A) were injected into the ventral subcu-