PHARMACOKINETIC AND CLINICAL STUDIES ON CEFODIZIMEIN THE PEDIATRIC FIELD

Abstract

A multi-center open study was conducted to investigate cefodizime (CDZM), a newly developed cephem antibiotic, 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 a bolus intravenous injection or intravenous drip infusion over 30 or 60 minutes. The results were nearly the same as those in adult patients.
Mean serum concentrations 5 minutes after a bolus intravenous injections were: 105.5, 264.0 and 461.7μg/ml with 10, 20 and 40mg/kg, respectively, and T1/2 (β)'s for the 3 dosages were 1.75, 1.92 and 1.88 hours, respectively.
With 30-minute intravenous drip infusion, mean serum concentrations at the end of infusion were: 90.5μg/ml with a dose level of 10mg/kg, 178.3μg/ml with 20mg/kg, and 322.8μg/ml with 40mg/kg, and T 1/2 (β)'s for these dosages were 1.90, 2.15 and 1.93 hours, respectively.
With 60-minute intravenous drip infusion, mean serum concentrations at the end of infusion were: 66.3μg/ml with a dose level of 10mg/kg, 136.0μg/ml with 20mg/kg and 259.2μg/ml with 40mg/kg, and T 1/2 (β)'s for these dosages were 1.43, 2.05 and 1.46 hours, respectively.
In 8 hours after administration of CDZM, urinary excretion rates were 82.1, 77.7 and 76.5% for bolus intravenous injections of 10mg/kg, 20mg/kg and 40mg/kg, respectively, and 83.3, 71.3and 68.1% for 30-minute intravenous drip infusions of 10mg/kg, 20mg/kg and 40mg/kg, and 84.4 and 84.3% for 60-minute intravenous drip infusions of 20mg/kg and 40mg/kg, respectively.
2. Concentrations in cerebrospinal fluid:
Penetrations into cerebrospinal fluid in patients with purulent meningitis reached levels of 1.96-9.48μg/ml with administration of CDZM at 50mg/kg in acute cases within 6 days after onset. The penetration rates of CDZM were about a median range among injectable β-lactamagents.
3. Clinical results:
Of 457 cases treated with CDZM, 53 cases were excluded from the clinical evaluation.
Clinical efficacies were evaluated as “excellent” in 126 and “good” in 78 out of 221 cases from which causative agents were isolated, with an efficacy rate of 92.3%. Efficacies were “excellent” in 97 and “good” in 69 out of 183 cases from which pathogens were not isolated, giving an efficacy rate of 90.7%.
With regard to microbiological effect on pathogens, 213 out of a total of 230 strains isolated as pathogens were eliminated with a high eradication rate of 92.6%.
Among Gram-positive bacteria, 31 out of 32 strains of Streptococcus pneumoniae were successfully eliminated with a high eradication rate of 96.9%. An excellent elimination activity of CDZM was also noted against Streptococcus pyogenes, with all 6 strains of this species were eliminated. On the whole, 64 out of 76 strains of Gram-positive bacteria were eliminated, giving an eradication rate of 84.2%.
For Gram-negative bacteria, the following causative microbes were eliminated including all the strains of Branhamella catarrhalis (15), Escherichia coli (21), Klebsiella pneumoniae (4), Haemophilus influenzae (82) and Proteus mirabilis (4). In total, 149 out of 154 strains of Gram-negative bacteria were eradicated with a very high eradication rate of 96.8%.
The clinical effects of the drug by causative agents were evaluated as “good” or “excellent” in 204 out of 221 cases with an efficacy rate of 92.3%. Noteworthy was the effectiveness of CDZM against mixed infections of 2 or 3 species; the drug was effective in 30 out of 33 cases, the rate being as high as 90.9%.