PHARMACOKINETIC AND CLINICAL STUDIES ON CEFUZONAM IN THE PEDIATRIC FIELD

Abstract

A multi-center open study was conducted to investigate cefuzonam (L-105, CZON), a newly developed cephalosporin from pharmacokinetic, bacteriological and clinical aspects, in the pediatric field with the participation of 17 institutions and their related facilities. The results are summarized as follows.
1. Serum concentrations and urinary excretion
The pharmacokinetics in pediatric patients was investigated with a dose of 20mg/kg, via one shot intravenous injection or intravenous drip infusion over 1 hour. The results were nearly the same as those in adult patients. Mean serum concentrations 5 minutes after one shot intravenous injections were: 52.8μg/ml with the dosage of 10mg/kg, 135μg/ml with 20mg/kg, and 317μg/ml with 40mg/kg, and T 1/2 β's for the 3 dosages were 1.07 hours, 0.91 hour, and 1.01 hours, respectively. With 1-hour intravenous drip infusion, mean serum concentrations at the end of infusion were: 22.4μg/ml with 10mg/kg, 46.3μg/ml with 20mg/kg, 72.5μg/ml with 40mg/kg, and 69.2μg/ml with 50mg/kg, and T1/2β's for these dosages were 1.31 hours, 1.45 hours, 0.84 hour, and 0.66 hour, respectively. In 6 hours after administration of CZON, urinary excretion rates were 43.5-51.4% for one shot intravenous injections of 10-40mg/kg, and 42.7-58.6% for 10-50mg/kg drip infusions.
2. Concentrations in cerebrospinal fluid
Penetrations into cerebrospinal fluids in patients with purulent meningitis achieved levels of 2.80-6.40μg/ml with the administration of CZON at 100mg/kg in acute cases of within 6 days after onset. When the administration of the drug was done at the earlier stage, the greater penetration occurred. However, rates of penetration were 3.10% to 5.03% within 4 days after a drug administration, thus, the penetration was not thought to be as good as other β-lactam agents which achieve higher penetration rates.
3. Clinical results
Of 407 cases treated with CZON, 18 cases were excluded from the statistical analysis. The remaining 389 cases plus 8 cases each of which had 2 complicated diseases, with a total of 397, were statistically analyzed for the clinical effectiveness of this drug against various infections.
The efficacy was evaluated as “good” or “excellent” in 248 out of 266 cases from which pathogens were isolated, for an efficacy rate of 93.2%. The efficacy rate was 88.5% for 131 cases for which pathogens were unidentified, thus no statistically significant difference was noted between the 2 groups. The overall efficacy was evaluated as “good” or “excellent” in 364 cases out of total 397 cases, for an efficacy rate was 91.7%.
With regard to microbiological effect on pathogens, 240 out of 268 strains isolated as pathogens were eliminated, for an elimination rate of 89.6%.
Among Gram-positive bacteria, 45 out of 53 strains of Staphylococcus aureus were successfully eliminated, for an elimination rate of 84.9%. An excellent elimination activity of CZON was also noted against Streptococcus pneumoniae and Streptococcus pyogenes. On the whole, 90 out of 101 strains of Grampositive bacteria were eliminated, for an elimination rate of 89.1%.
For Gram-negative bacteria, the following causative microbes were eliminated including all the strains of Escherichia coli (49) and Klebsiella pneumoniae (5), 2 out of 3 strains of Proteus mirabilis, and 88 strains, or 90.7%, of 97 Haemophilus spp. strains. Out of a total of 154 strains of the 4 genera, 144 were eliminated, the elimination rate being as good as 93.5%. In total, 150 out of 164 strains of Gram-negative bacteria were eradicated, and the eradication rate was 91.5%.
The clinical effects of the drug on pathogens were evaluated as “good” or “excellent” in 266 out of 248 cases, for an efficacy rate of 93.2%.