[Pharmacokinetic, bacteriological and clinical studies on cefozopran in the pediatric field].
Cefozopran (CZOP, SCE-2787), a newly developed parenteral cephem antibiotic, was administered to children with bacterial infections. We determined its antibacterial activity, pharmacokinetics, efficacy and safety in these patients. 1. Antibacterial activity MICs of cefmetazole, ceftazidime, cefuzonam, flomoxef and CZOP were determined against a total of 19 strains. For Gram-positive cocci, MICs of CZOP ranged from 0.39 to 0.78 microgram/ml against Staphylococcus aureus (3 strains), from 0.05 to 6.25 micrograms/ml against Streptococcus pneumoniae (5 strains), and 12.5 micrograms/ml against Enterococcus faecalis (1 strain). These MICs were generally similar to those of other cephems, but the MIC of CZOP against E. faecalis was lower than those of the other cephems examined. For Gram-negative bacilli, MICs of CZOP were 25 micrograms/ml against Citrobacter freundii (1 strain), and 6.25 micrograms/ml against Pseudomonas aeruginosa (1 strain). These values were similar to or lower than those of other cephems, MICs of CZOP against Haemophilus influenzae (7 strains) ranged from 0.1 to 0.39 microgram/ml. However, the MIC of CZOP against Serratia marcescens (1 strain) was higher than 100 micrograms/ml, and CZOP was as ineffective as the other cephems against this organism. 2. Pharmacokinetics CZOP was administered to children at 20 or 40 mg/kg via intravenous injection, and determinations were made for its serum concentrations, urinary concentrations and concentrations in cerebrospinal fluid (CSF) using the bioassay. Serum concentrations at 30 minutes after administration were 60.4 micrograms/ml with a dose of 20 mg/kg to one patient and 93.9 and 99.0 micrograms/ml with 40 mg/kg to two patients. The corresponding half-lives were 1.55 hours for 20 mg/kg administration, and 1.10 and 3.41 hours for 40 mg/kg, while the AUCs were 136.5 micrograms.hr/ml for 20 mg/kg, and 194.4 and 264.5 micrograms.hr/ml for 40 mg/kg. The rates of urinary recovery in the first 8 hours after administration were 45.0% in the patient receiving 20 mg/kg, and 84.6 and 97.6% in the two patients receiving 40 mg/kg. The concentrations in the CSF determined in 3 patients with purulent meningitis ranged from 2.6 to 16.0 micrograms/ml 1 hour after administration, and the CSF/serum concentration ratio ranged from 6.5 to 39.0%. These values for pharmacokinetic parameters obtained in the bioassay were similar to those obtained using HPLC. 3. Clinical evaluation Forty-eight patients were clinically evaluated. Of these patients, 75% were less than 3 years of age and there were slightly more male children than female children.(ABSTRACT TRUNCATED AT 400 WORDS)
Department of Pediatrics, School of Medicine, Kurume University.
T
T
Motohiro
S
S
Handa
S
S
Yamada
H
H
Sasaki
S
S
Oki
Y
Y
Yoshinaga
K
K
Oda
M
M
Aramaki
Y
Y
Sakata
F
F
Yamashita
D001419:Bacteria / Q000187:drug effects / Q000302:isolation & purification; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D002511:Cephalosporins / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004352:Drug Resistance, Microbial; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D000097586:Cefozopran
D002511:Cephalosporins; D000097586:Cefozopran