Sulfamethoxazole-Trimethoprim合剤に関する基礎的ならびに臨床的研究

抄録

1. Potentiation of in vitro antimicrobial activities of sulfamethoxazole (SMX) and trimethoprim (TMP) combined at ratios of 10 : 1 and 20 : 1 were demonstrated in Staphylococcus aureus FDA 209P JC-1, Escherichia coli NIHJ JC-2 and other strains of Staphylococcus aureus and Escherichia coli isolated from clinical materials.
2. This combination product is well absorbed after oral dosing followed by satisfactory renal excretion. Concentrations of 2 active drugs were maintained over a relatively long period of time and concentrations in the urine were high.
3. Studies on the distribution of the 2 drugs in rat revealed that SMX concentrations in the blood were higher by several times than those found in the liver, kidney and lung, whereas those of TMP in the blood were lower by several times than those in the liver, kidney and lung, indicating an extensive extra-vascular distribution of the latter compound. The ratio of SMX and TMP concentrations varied according to the kind of tissue, organ and the time interval after drug administration.
4. The in vitro antimicrobial activity of 4-demethyl-TMP, a metabolite of TMP, was found to be essentially similar to that of the parent compound. Thin layer chromatography failed to detect this metabolite in 10-fold concentrated human urine specimens collected 8 hours after a dose of 800 mg SMX and 160 mg TMP. It was assumed that concentrations of this metabolite in the urine were not probably exceeding 10 mcg/ml.
5. SMX-TMP combination products were given to 6 patients with urinary tract infections. In 5 patients urine cultures became sterile and a significant reduction of bacterial count was recorded in another. However, bacteriological relapse and superinfections were observed in 3 patients after cessation of the drug therapy. Fever and eruption possibly related to therapy were encountered in a single patient.