Abstract
Bacteriological, pharmacokinetic and clinical studies on cefdinir (CFDN, FK482), a new oral cephalosporin, 5% and 10% granules, were performed in the field of pediatrics. The results are summerized below.
1. Antibacterial activities
Antibacterial activities of CFDN against Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis, Escherichia coli and Klebsiella pneumoniae were studied in comparison with those of cefaclor (CCL), cefixime (CFIX) and amoxicillin (AMPC). MIC80's of CFDN against S. aureus, S. pneumoniae, S. pyogenes, H. influenzae, B. catarrhalis, K. pneumoniae and E. coli were 0.78, 0.20≤0.025, 0.39, 0.10, 0.20 and 0.10 μg/ml, respectively. These results show that CFDN has high antibacterial activities against these organisms. MIC80's of CFDN against Gram-positive bacteria were similar to those of AMPC, and was lower than those of CCL and CFIX. As for antibacterial activities against Gram-negative bacteria (GNB), the MICgo of CFIX against H. influenzae was 0.05, μg/ml, which was slightly lower than tht of CFDN. The MIC80's of CFDN against other GNB were similar to those of CFIX.
2. Absorption and excretion
Blood concentrations and urinary excretion rates of CFDN 5% and 10% granules and 100 mg capsule were determined. The data on CFDN 10% granules Were similar to those on CFDN 5% granules. At a dose of 3mg/kg, peak blood concentrations (Cmax's) of CFDN ranged from 0.20 to 2.12, μg/ml with 5% granules and from 0.50 to 1.15 μg/ml with 10% granules at 2 to 3 hours after dosing. At a dose of 6mg/kg, peak concentrations were 0.66-2.06 μg/ml and 0.70-1.52 μg/ml with 5% granules and with 10% granules, respectively. At 8 hours after dosing, blood concentrations were 0.04-0.54 μg/ ml at 3mg/kg and 0.06-0.27 μg/ml at 6mg/kg. Blood half-lives were 1.33-4.36 hours at 3 mg/ kg and 1.14-3.27 hours at 6mg/kg. AUC's were 1.7-11.0μg·hr/ml with 3mg/kg and 2.4-8.7 μg·hr/ml with 6mg/kg. With administration of single 100 mg capsule, Cmax's, blood concentrations after 8 hours, T 1/2's and AUC's were 0.79-1.88μg/ml, 0.20μg/ml, 1.54-2.72 hours, and 5.2 μg·hr/ml, respectively. Urinary recovery rates in the first 8 hours ranged from 6.85 to 39.2% with 3mg/kg and 6.08-25.5% with 6mg/kg.
3. Clinical study
Clinical efficacies were examined in a total of 76 cases consisting of 9 cases of acute pneumoniae, 11 of bronchitis, 23 of purlent tonsillitis, 15 of scarlet fever, 8 of acute lymphadenitis, 2 of phlegmon, one of subcutaneous abscess, one of impetigo and 6 of UTI. Clinical efficacy rate was 98.7% (74/75), and bacteriological eradication rate was 98.6% (69/70). As for side effects, watery stools and an elevation of GPT were noted.
