Laboratory and clinical studies on clarithromycin in pediatrics

The antibacterial activity of TE-031 was investigated against 16 clinically isolated strains of Streptococcus pyogenes, Staphylococcus aureus, Haemophilus influenzae, Bordetella pertussis and Campylobacter jejuni. TE-031 showed antibacterial activity comparable to erythromycin. The pattern of changes in TE-031 concentrations in the blood after administration was investigated. In subjects administered the granular preparation of TE-031, C(max) values were 0.64 μg/ml in 1 subject given a 5 mg/kg dosage, and 5.94 and 9.02 μg/ml in 2 subjects administered with 10 mg/kg. The tablet form of TE-031 was administered to 3 subjects at 5 mg/kg, and C(max) values were 2.09 ~ 3.92 μg/ml, while T 1/2 values were in a range of 2.9 ~ 3.8 hours. When drug concentrations in the urine were investigated, it was found that 6-hour recovery rates were 9.9% (dose: 5 mg/kg) and 53.4% (dose: 10 mg/kg) in the subjects administered the granular form, whereas recovery rates averaged 36.8% in the tablet-administered subjects. In the clinical trial, TE-031 was administered in 2 ~ 3 doses/day for 2 ~ 18 days. In cases given the granular form, dosages were 12 ~ 38 mg/kg/day, while tablets were administered at 12 ~ 29 mg/kg/day. The overall clinical efficacy rate was 92.8%, i.e., the drug was effective in 64 of 69 patients. TE-031 was ineffective in 1 case of otitis media, but efficacious in 10 of 10 (100%) cases of upper respiratory infection, 15 of 18 (83.3%) cases of bronchitis and pneumonia, 5 of 6 (83.3%) cases of pertussis, 13 of 13 (100%) cases of mycoplasmal pneumonia, 4 of 4 (100%) cases of Chlamydia psittaci pneumonia, 16 of 16 (100%) cases of gastroenteritis (including 15 cases of Campylobacter gastroenteritis), and 1 (100%) case of impetigo. In bacteriological studies conducted on the patients, the overall elimination rate was 93.1%, i.e., bacterial elimination was obtained in 27 of 29 cases. TE-031 showed especially good bacteriological efficacy (100%) against C. jejuni and B. pertussis, which were eliminated from all of 15 and 2 cases examined, respectively. Analysis for side effects was conducted in 82 patients administered with TE-031. Adverse symptoms occurred in 6 of those patients, for an incidence rate of 7.3%. These side effects consisted of digestive tract symptoms in 5 patients (1 case each of abdominal pain, vomiting, and abdominal pain and vomiting, and 2 cases of diarrhea or loose stool) and urticaria in 1 patient. Various laboratory test abnormalities were also detected: eosinophilia in one of 38 (2.6%) patients examined, elevated GOT in 3 of 39 (7.7%) patients, and elevated GOT and GPT in one of 39 (2.6%) patients. In addition, studies were carried out to determine whether or not TE-031 exerts any effect on the hemostatic mechanism, but no change was detected in the blood clotting factors by the TE-031 administration regimen. On the basis of the basic and clinical study results summarized above, it is surmised that TE-031 will be an effective and safe oral antibiotic for use in the treatment of infections in children when administered 2 ~ 3 times per day in a dose of 5 ~ 10 mg/kg.