EVALUATION OF CHEMOPROPHYLACTIC ACTIVITY BY THE SUBCUTANEOUS IMPLANTATION OF PELLETS OF SULFONAMIDES IN MICE

¹ Department of Pharmacology, Medical Research Division, Sharp and Dohme, Inc., Glenolden, Pennsylvania

A method of implanting pellets of sulfonamide in mice is described by means of which a very gradually decreasing concentration of drug is maintained in the blood. This method, particularly useful with the more slowly excreted sulfonamides, affords a simple means for evaluating the activity of a sulfonamide in protecting against various bacterial infections. A comparative study of sulfamerazine and sulfadiazine indicated that for equivalent concentrations of drug in the blood to be maintained, twice as many pellets of sulfadiazine as of its mono-methyl derivative, sulfamerazine, must be implanted. The concentration of free drug found necessary for protection of 50 per cent of mice against lethal hemolytic streptococcal infection, was for sulfadiazine, 0.8, and for sulfamerazine, 2.4 mgm. per 100 cc. of blood; this difference between the two drugs was seen only at critically low blood levels, since the concentrations required to protect 100 per cent of mice did not differ. Against lethal pneumococcal (Type I) infection, the concentration for protection of 50 per cent of mice was for sulfadiazine, 16.4, and for sulfamerazine, 14.8 mgm. per 100 cc. of blood.