Abstract
Pharmacokinetic, bacteriological, and clinical studiesoncefdinir (CFDN, FK482)(10% fine granules), a new oral cephem, were performed in pediatrics.
1.Bioequivalencies of plasma concentrations and urinary excretions of CFDN 5% and10% fine granules were investigated on 3 pediatric patients with ages between 5 to 13 years administered with a drug in fasting state at a dose level of 3mg/kg using a cross over method.Average plasma concentrations in a group of patients administered with 5% fine granules peaked at 3 hours after administration with a level of 1.05±0.29μg/ml (mean±S.E) and decreased to 0.12±0.05μg/mlat 8 hours with a half-life of 1.48±0.09 hours.In the group administered with 10%fine granules, average plasma concentrations peaked at 2 hours after administration with a level of 1.32±0.12μg/ml, and decreased to 0.20±0.11μg/ml at 8 hours with a half-life of 1.68±0.28 hours. The first 8-hour urinary recovery rates of CFDN in the 5% and 10% fine granules groups averaged 19.64± 5.69% and 23.37±2.36%, respectively.
Both average and individual plasma concentrations and urinary recovery rates in the patients of the 10% fine granules group were somewhat higher than those of the 5% fine granules group, but no significant differences were observed between the 2 groups including areas under concentrations.
2. CFDN 10% fine granule preparation was administered to 33 pediatric patients with ages between 1 to 13 years with various infections, and its clinical effects, bacteriological effects and safety were assessed.
In 31 of the 33 patients (2 patients were excluded since they were with non-bactedal infections) clinical effects were excellent in all of 9 patients with scarlet fever (3), acute pharyngitis (3) or impetigo (3), excellent in 12 and good in 3 of 15 patients with acute purulent tonsillitis, and excellent in 4 and good in 3 of 7 patients with acute pneumonia. The overall efficacy rate was 100%.
Bactedological effects against causative organisms were evaluated. All the identified Staphylococcus aureus (4 strains) and Streptococcus agalactiae (1) were eradicated. Of 10 strains of Strettococcus pyogenes, 9 strains were eradicated and the other one was reduced. Of 7 strains of Haemophilus influenzae 4 were eradicated, 1 persisted and the fate of the remaining 2 were unknown. The overall eradication ratewas 90.0%. Microbial substitutions were observed in 5 patients. The new, replacing bacteria were all Haemothilus spp. Diarrhea was noted in 4 patients, but no other side effects nor abnormal laboratory tests results were observed.
One patient complained of difnculty in intaking the oral drug. No other compliance problems were noted with this drug.
In conclusion, CFDN 10% fine granule preparation was considered to be effective and safe in the treatment of pediatric infections, the outcome was similar to that with 5% fine granules.
