[Pharmacokinetic and clinical studies with cefozopran in the pediatric field. Pediatric Study Group of Cefozopran].
We investigated pharmacokinetics and clinical effectiveness of a newly developed cephem antibiotic cefozopran (SCE-2787, CZOP) against various pediatric infections in 18 institutions and their affiliates. We obtained the following results. 1. Serum concentration and urinary excretion rates Pharmacokinetics of CZOP in children was examined after intravenous injection and 30-minute drip infusion of 10, 20 and 40 mg/kg of CZOP. Peak serum concentrations of CZOP in 30 minutes after intravenous injection were 21.7, 51.5 and 77.8 micrograms/ml, respectively, showing a clear dose response. Half-lives were 1.99, 1.85 and 1.67 hours, respectively. In the first 6 hours after administration, urinary excretion rates of CZOP were 87.3, 67.4 and 84.1%, respectively. In the cases of 10, 20 and 40 mg/kg administration of CZOP 30-minute drip infusion, peak serum concentration of CZOP in 30 minutes, when the infusion was completed, were 38.1, 72.8 and 95.6 micrograms/ml, respectively. Again, there was a clear dose response. Half-lives were 1.67, 1.69 and 1.43 hours, respectively. In the first 6 hours after administration, urinary excretion rates of CZOP were 53.9, 59.7 and 77.3%, respectively. Cerebrospinal fluid concentrations of CZOP administered by intravenous injection of 50 mg/kg to patients with purulent meningitis were 1.6 to 43.4 micrograms/ml in 1 to 1.5 hours after administration. 2. Clinical study Clinical efficacy was evaluated in 337 cases. The largest number of cases, 138 cases, were found in 2 to < 6-year olds. The majority of the patients were under age 9, and 70 cases were of less than 1-year old infants. 183 cases were males and 154 cases were females. In terms of illness, a majority, or 185 cases, suffered from pneumonia, followed by 39 cases of UTI and 23 infections of the skin and soft tissue. There were 7 cases of purulent meningitis. In 218 cases, CZOP was administered at a daily dose of 60- < 80 mg/kg. The drug was administered for 6-10 days, the most frequent duration, in 188 cases. In the cases where causative organisms were identified (group A), the efficacy rates ("excellent" and "good") obtained were 100% (5/5) against purulent meningitis, 100% (2/2) against sepsis, 98.3% (119/121) against pneumonia, 100% (13/13) against acute bronchitis, 100% (11/11) against upper respiratory tract infection, 96.3% (26/27) against UTI. Overall, "excellent" and "good" responses were observed in 97.5% (197/202) of cases with known causative organisms.(ABSTRACT TRUNCATED AT 400 WORDS)
Fujii
R
R
School of Medicine, Teikyo University.
Abe
T
T
Tajima
T
T
Terashima
I
I
Meguro
H
H
Nakazawa
S
S
Sato
H
H
Niinou
K
K
Sunakawa
K
K
Yokota
T
T
D000293:Adolescent; D001419:Bacteria / Q000187:drug effects / Q000302:isolation & purification; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D002511:Cephalosporins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003967:Diarrhea / Q000139:chemically induced; D003875:Drug Eruptions / Q000209:etiology; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D016920:Meningitis, Bacterial / Q000188:drug therapy; D012141:Respiratory Tract Infections / Q000188:drug therapy; D014552:Urinary Tract Infections / Q000188:drug therapy; D000097586:Cefozopran
D002511:Cephalosporins; D000097586:Cefozopran