Dose-finding study of S-1108 in chronic respiratory tract infections

To investigate the appropriate clinical dose of S-1108, a new ester-type oral cephem antibiotic, in the treatment of chronic respiratory tract infections excluding diffuse panbronchiolitis, we conducted dose-finding studies using cefteram pivoxil (CFTM-PI) as a reference drug at collaborating institutions. Daily doses were S-1108 450 mg (S450 group), S-1108 600 mg (S600 group) and CFTM-PI 600 mg (C600 group) divided into three equal doses for 14 days. The clinical responses were as follows : 1) The number of patients assessed by the investigator was 55 (S450 group : 19, S600 group : 19, C600 group : 17). The number of patients in which clinical efficacy was evaluated by the committee was 46 (S450 group : 14, S600 group : 17, C600 group : 15). The number of patients in which side effects were evaluated was 55 (S450 group : 19, S600 group : 19, C600 group : 17), The number of patients in which laboratory findings were evaluated was 52 (S450 group : 17, S600 group; 19, C0OO group : 16), The number of patients in which the utility of the drug was reported was 48 (S450 group : 16, S600 group; 17, C600 group; 15), 2) The clinical efficacy rates (“good” or better) judged by the committee were 85.7% for S450 group, 94.1% for S600 group and 73.3% for C600 group, with no significant differences among the three groups. 3) There were significant difference among the three groups with respect to the degree of improvement in cough (C600 group > S450 group) and WBC (S450 group, S600 group > C60Q group). 4) The number of patients judged as an elimination of causative organism were 6 out of 7 on S450 group, 7 of 10 on S600 group and 3 of 5 on C600 group, with no significant differences among the three groups. 5) Side effects were observed in 2 patients (10.5%) on S450 group, 2 patients (10.5%) on S600 group and 1 patient (5.9%) on C600 group. Abnormal changes in laboratory findings were also observed in 1 patient (5.9%) on S450 group, 1 patient (5.3%) on S600 group andl patient (6.3%) on C600 group. There were no significant differences among the three groups which regard to either of these items, 6) The satisfactory rate (“satisfactory” or better) judged by the committee was 75% for S450 group, 82.4%% (14/17) for S600 group and 73.3% (11/15) for C600 gorup, with no significant differences in incidence among the three groups. On the basis of these clinical results, we concluded that S-1108, 150mg, three times a day is an appropriate clinical dose in the treatment of chronic respiratory tract infections.