부산대학교 도서관

Pharmacokinetic, bacteriological and clinical studies on SY5555, a new oral penem, were carried out, and the following results were obtained.1. MICs were determined for 6 drugs, SY5555, clavulanic acid/amoxicillin (CVA/AMPC), cefaclor (CCL), cefotiam (CTM), cefpodoxime (CPDX), cefdinir (CFDN) against 20 strains of bacteria isolated from patients who were subsequently treated with SY5555. MICs of SY5555 for Gram-positive cocci ranged from 0.05 to 0.10μg/ml against 10 strains of Staphylococcus aureus. The MIC was≤0.025μg/ml against one strain of Streptococcus pyogenes, and MICs were from ≤0.025 to 0.39μg/ml against streptococcus pneumoniae. These MIC values were equivalent or superior to those of the other 5 drugs. MICs of SY5555 for Gram-negative bacilli were 0.39 and 6.25μg/ml against Haemophilus influenzae, and these values were equivalent to those of the other drugs, except CPDX. The MIC of SY5555 was 0.39μg/ml against 2 strains of Escherichia coli, and this value was equivalent or superior to those of CVA/AMPC and CCL, similar or inferior to those of CPDX and CFDN, and inferior to that of CTM. The MICs of several drugs were determined for 10 strains of Bordetella pertussis and 30 strains of Campylobacter jejuni isolated from patients before this clinical study. The MICs of SY5555 against the 10 strains of B. pertussis were compared with those of 7 drugs, CCL, CTM, CPDX, ampicillin (ABPC), piperacillin (PIPC), imipenem (IPM) and erythromycin (EM). The MIC of SY5555 was 0.78μg/ml against all of the strains. This value was superior to those of CCL, CTM and CPDX, similar or inferior to that of IPM and inferior to those of PIPC and EM. The MICs of SY5555 against the 30 strains of C. jejuni were compared with those of 7 drugs. CCL, CTM, CPDX, CFDN, ABPC, IPM and EM, and the MIC of SY5555 was≤0.025μg/ml or 0.05μg/ml and these values were equivalent or superior to those of the 7 reference drugs.2. SY5555 dry syrup was administered orally at 30 min. after meals, to a total of 5 patients, at doses of 5.0 and 10.0 mg/kg to 2 patients each and at a dose of 15.0 mg/kg to one patient and the plasma concentrations were determined. Peak concentrations were detected 1 to 3 hours after administration in all patients and the peak concentrations were 0.93 and 1.21μg/ml at the 5.0 mg/kg dose, 2.85 and 5.49μg/ml at the 10.0 mg/kg dose and 5.79μg/ml at the 15.0 mg/kg dose. A dose-response relationship was observed among the three dose groups, except one of the patient who received the 10.0 mg/kg dose had a high plasma concentration, and the half-lives in all of the patients ranged from 0.76 to 1.05 hours. AUCs also showed a dose-response relationship in the three dose groups, except for the patient who received the 10.0 mg/kg dose and showed a high plasma concentration level.3. Urinary concentrations were determined in the above patients and peak urinary concentrations occurred in 0 to 2 hours in one patient and in 2 to 4 hours in 4 patients. Urinary recovery rates in the first 6 hours after administration ranged from 6.0 to 13.8%.4. SY5555, mainly in dry syrup (powder dissolved just before use), was administered to children with infectious diseases. Clinical efficacies in the 76 evaluable patients were excellent in 20, good in 43, fair in 9 and poor in 4, and the overall efficacy rate was 82.9%.5. Bacteriologically, 33 causative organisms were identified in the above clinical study, and 30 were eradicated. The eradication rate was 90.9%.6. Side effects were evaluated in 82 patients and diarrhea was reported in 4.7. No abnormal changes in laboratory test values were noted, except for an increase in eosinophil count in one patient.