Abstract
In vitro and clinical studies were performed on ceftazidime (CAZ, SN 401). CAZ has a broad spectrum of antibacterial activity. CAZ has a slightly narrower spectrum than CMZ against Gram-positive, but a wider spectrum against Gram-negative bacilli. Its antibacterial activity against clinical isolates S. aureus and S. epidermidis, was inferior to the other cephalosporins and cephamycin antibiotics but stronger against E. coli, K. pneumoniae, P. rnirabilis, S. marcesceas, Enterobacter and P. aeruginosa.
It also had stronger antibacterial activity against B. fragilis than CMZ.
Serum and urine concentrations of CAZ were determined in 3 healthy adults using bioassay and HPLC after a 1.0 g i. v. injection. Serum concentrations 5 min. after administration averaged 101μg/ml (bioassay) and 117μg/ml (HPLC), and after 10 hrs., 0.79μglml (bioassay) and 0.6μg/ml (HPLC).
The peak urinary level was reached 30 min. after administration and averaged 6, 834μg/ml (bioassay) and 8, 000μg/ml (HPLC).
The urinary recovery rate up to 10 hrs. was 85.8%(bioassay) and 99.9%(HPLC). Serum concentration of CAZ determined by HPLC were investigated from the viewpoint of pharmacokinetics, and the results were K12 (hr-1): 0.78, K21 (hr-1): 1.26, Kel (hr-1): 0.90, T 1/2 (β)(hr.): 1.51, AUC (hr. ml): 1.44.
In vivo metabolism of CAZ was examined using human urine with bioautography and TLC and it was found that CAZ was excreted without being metabolized.
The concentration of CAZ after an intramuscular injection of 20mg/kg in SD rats was found to be the highest in the kidney, follwed by the serum, lungs, heart spleen, and liver, and lowest in the muscles.
Clinical response to CAZ in 35 cases of surgical infections was evaluated as excellent in 5 cases, good in 25, poor in 4 and unassessable in 1.
Side effects were as follows: elevation of GOT in 1 case, elevation of GPT in 3 cases, elevations of both GOT and GPT in 1 case, and vomiting in 1 case.
