Minimum inhibitory concentrations (MICs) of sulfamethoxazole (SMX) and trimethoprim (TMP), alone and in 20 : 1 combination were studied employing agar plate dilution method with MUELLER-HINTON agar (pH 7.4) in 22 laboratory strains of Escherichia coil. Lysed horse blood was added to the assay medium. In the majority of strains MICs of SMX were higher than 200 mcg/ml of SMX, however, MICs of TMP, were always within the range between 0.8 and 0.05 mcg/ml, with the mode at 0.02 mcg/ml. MICs of the combination of SMX and TMP ranged between 6.3 and 0.4 mcg/ml. Potentiation of antimicrobial activities was clearly demonstrated by combining the 2 drugs in some strains but in others the degree of potentiation was slight or absent.
Concentrations of SMX and TMP in serum and urine following 2 and 4 tablets of SMX-TMP combination preparation (1 tablet contains 400 mg SMX and 80 mg TMP) were determined in human subjects known to have no renal impairment. The peak plasma level of TMP after 2 tablets was attained in 4 hours, averaging 2. 7 mcg/ml and that of SMX in 6 hours, averaging 62 mcg/ml for free-SMX and 78 mcg/ml for total SMX. Concentration in the urine varied between 10 and 50 mcg/ml for TMP, and between 40 and 300 mcg/ml for free-SMX. Levels obtained in a patient given 4 tablets were correspondingly higher. Concentration ratios of SMX and TMP in the serum ranged between 20-40 : 1 while those in urine specimen 4-10 : 1, indicating different metabolic pathways of the 2 drugs in vivo.
Concentrations of SMX and TMP in rat tissues following oral application of SMX-TMP were determined. The results indicated higher extravascular distribution of TMP while tissue concentrations of free-SMX were approximately similar to serum levels.
The binding of TMP to serum proteins was found to be less than 10% whether existing alone or in combination with SMX.
