PHARMACOKINETICS AND CLINICAL EFFECTS OF CEFDINIR 10% FINE GRANULES IN PEDIATRICS

Abstract

Cefdinir (CFDN), a newly developed oral cephalosporin in a 10% fine granular form, was administered to 8 children and concentrations of the drug in plasma and urine and urinary recovery rates of the drug were determined. The subjects were divided into 2 groups of 4 children each; one group received 3mg/kg of CFDN at 1 hour before meal (in the fasting state), and the other, at 30 minutes after meal.
To study clinical and bacteriological effects of this drug, a mean dose of 4.8mg/kg t.i.d. was administered for 8 days on the average to 9 children with various infections; tonsillitis (3 cases), acute bronchitis (1), pneumonia (1), acute purulent otitis media (1), urinary tract infection (2), and impetigo (1). MICs were determined for 6 drugs including CFDN, cefaclor, cefixime (CFIX), methicillin, cloxacillin, amoxicillin (AMPC) against 4 strains freshly isolated from children receiving CFDN. An inoculum size of 10⁶ cfu/ml was used in the MIC-determinations.
Adverse reactions and abnormal laboratory findings attributable to this drug were also examined in these children.
The results obtained are summerized as follows.
1. Mean plasma peak levels of CFDN were observed at 2 hours after administration in the before-meal group and 4 or 5 hours after administration in the after-meal group mean peak values of 0.88 and 0.50μg/ml, respectively. Mean half-lives were 1.61 hours in the before-meal group and 2.54 hours in the after-meal group, and mean AUCs were 4.24 in the former and 3.59μg·hr/ml in the latter.
2. Mean urinary peak concentrations of CFDN were observed during 2-4 hours after dosing in the before-meal group and during 6-8 hours in the after-meal group with values of 93.3 and 44.8μg/ml, respectively, in cases for which plasma concentrations of drugs were determined. Mean urinary recovery rates during the first 8 hours after administration in the before-and after-meal groups were 16.6 and 13.4%, respectively.
3. Good clinical effects were obtained with an efficacy rate of 100% in 9 patients with 6 diseases due to bacterial infections.
4. Good bacteriological effects were also obtained against 2 strains of Streptococcus pyogenes, 2 strains of Escherichia coli and 1 strain of Haemophilus influenzae with an eradication rate of 100%. In 3 cases of these and another case (normal flora), strains present before the study were replaced by other strains.
5. MICs of CFDN against 2 freshly isolated strains of S. pyogenes were similar to or higher than those of AMPC and similar to lower than those of the other 4 drugs tested. MICs of CFDN against 2 freshly isolated strains of E. coli were almost the same as those of CFIX and similar to or lower than those of the other 4 drugs.
6. No adverse reaction nor abnormal laboratory finding due to this drug was observed in 9 patients.