Abstract
1. Seven healthy male volunteers received either ceftazidime (CAZ, SN401) and cefotiam (CTM) or CAZ and cefoperazone (CPZ) in a cross over method for the comparative study on pharmacokinetics. All the drugs were administered intravenously.
1) Four of the volunteers received each 1g of CAZ and CTM by intravenous bolus. The beta half lives were 1.50 hrs for CAZ and 0.94 hr for CTM, and the urinary recovery rates up to 8 hrs were 91.5% and 72.9%, respectively. Semen concentrations of CAZ and CTM at 8 hrs were 1.46μg/ml and 1.16μg/ml respectively, and at 24 hrs the concentration of CAZ was 0.42μg/ml but CTM was not detected.
2) Five of the volunteers received each 1g of CAZ and CTM by drip infusion for 30 min. The peak serum concentrations of CAZ and CTM were 77.8μg/ml and 61.3μg/ml, the beta serum half lives, 1.60 and 0.96 hr, and the urinary recovery rates up to 12 hrs were 76.3 and 65.2%, respectively.
3) Five of the volunteers received CAZ in the doses of 0.5g and 1g, and CPZ at 1g, by drip infusion for 30 min. The peak serum concentrations were 42.6μg/ml, 92.1μg/ml and 102.4μg/ml, the beta serum half lives were 1.49, 1.66 and 1.74 hrs, and the urinary recovery rates up to 12 hrs were 91.8%, 83.1% and 27.2%, respectively.
Urine samples were collected every 2 hrs in the above studies 2) and 3), for the study on antibacterial activity of these antibiotics in the urine. As the test organisms, E.coli and K. pneumoniae, both with comparable sensitivity to CAZ and CTM, were used in the study 2), and E. coli and P. aeruginosa, which show comparable sensitivity to CAZ and CPZ, in the study 3). Comparison of the bacterial growth inhibitions in various dilutions of urine samples revealed that CAZ had the highest antibacterial activity in the urine. This is considered to be partly due to comparatively short half life of CTM and to the low urinary recovery rate of CPZ.
2. CAZ was administered intravenously to 2 male rabbits, one dehydrated and the other overhydrated, in the dose of 1g, and the drug concentrations in serum and organ tissues were determined. On the whole, CAZ concentrations were higher in the dehydrated rabbit, and particularly high in its testis and prostate gland.
