PHARMACOKINETIC AND CLINICAL STUDIES ON CEFOZOPRAN IN THE FIELD OF PEDIATRICS

• Published in: Japanese journal of antibiotics 1994/11/25, Vol.47(11), pp.1565-1575
• Main Authors: KAINO, YUKIKAZU, KIDA, KAICHI, MATSUDA, HIROSHI
• Format: Article
• Language: Japanese
• Subjects: Bacteria - drug effects; Bacteria - isolation & purification; Bacterial Infections - drug therapy; Bacterial Infections - metabolism; Bacterial Infections - microbiology; Cefozopran; Cephalosporins - pharmacokinetics; Cephalosporins - pharmacology; Cephalosporins - therapeutic use; Child; Child, Preschool; Drug Resistance, Microbial; Female; Humans; Infant; Injections, Intravenous; Male
• ISSN: 0368-2781; 2186-5477
• DOI: 10.11553/antibiotics1968b.47.1565

Blood and urine levels of cefozopran (CZOP) were determined, and its efficacy and safety profile was evaluated in the field of pediatrics. The results of this study are summarized as follows. 1. Blood levels of CZOP peaked in 30 minutes to 1 hour (initial blood collection) after intravenous administration at a dose of 20 or 40mg/kg. Its blood levels at 6 hours after intravenous administration were 1.6μg/ml (HPLC) or 1.9μg/ml (bioassay) at a dose of 20mg/kg and 2.9 to 9.1μg/ml (HPLC) or 2.9 to 8.4μg/ml (bioassay) at a dose of 40mg/kg. The half-lives were 1.58 to 2.27 hours (HPLC) and 1.53 to 1.85 hours (bioassay), respectively. The rate of recovery of CZOP in the urine in the first 8 hours after intravenous administration at a dose of 20mg/kg was 61.5% (HPLC) or 54.6% (bioassay), and urine levels of CZOP at 6 to 8 hours after administration were 157.3μg/ml (HPLC) and 129.7μg/ml (bioassay). 2. When CZOP was administered to 16 patients with respiratory tract infections, 2 patients with urinary tract infections, 2 patients with acute enteritis, 1 patient with skin soft tissue infection, and 1 patient with purulent lymphadenitis, the responses were excellent in 68% of patients and good in 32% with an overall efficacy rate of 100%. 3. Bacteriological effect of CZOP was excellent and the rate of bacterial eradication was 100% (9/9). 4. MICs of CZOP against clinical isolates (Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Streptococcus pneumoniae, Escherichia coli, Moraxella (Branhamella) catarrhalis) were compared to those of other injectable cephems ceftazidime (CAZ), cefuzonam (CZON), flomoxef (FMOX), cefmetazole (CMZ). The MICs of cefozopran (CZOP) against Gram-positive organisms, S. aureus, MRSA, and S. pneumoniae, were nearly as low as those of CZON and were clearly lower than those of CAZ. MICs of CZOP against Gram-negative organisms were examined and the MIC against E. coli was as low as those of other antibiotics but the MIC of CZOP against M.(B.) catarrhalis was higher, at 1.56μg/ml, than those of CAZ, FMOX, and CMZ. 5. Diarrhea was experienced by 1 of 22 patients as a side effect from CZOP, and abnormal laboratory tests including increases of eosinophil counts in 2 patients (9.1%), a decrease of neutrophil counts in 1 patient (4.5%), thrombocytosis in 1 patient (4.5%), and an elevation of GPT in 3 patients (13.6%). These events were all so mild that they had no clinical implications. Based on the results presented, it may be reasonably c