Pharmacokinetics of multiple doses of ceftizoxime and their influence on fecal flora

Abstract

The pharmacokinetics of ceftizoxime, a new β-lactam antibiotic, were studied in eight normal volunteers after single and multiple i.v. doses of 2×2 g daily for eight days. The mean maximum serum concentration after the first 20 min of infusion on the first day was 176.9 ± 32.9 μg/ml decreasing to 11.0 ± 4.1 μg/ml after 4 h and to 0.67 ± 0.2 μg/ml after 12 h. Mean 12 h urine recovery was 78.8 ± 9.0 %. The half-life of ceftizoxime was 136 ± 36 min. Volume of distribution was 22.9 ± 8.1 1/100 kg body weight, AUC_tot 208 ± 33 μg/ml · h, total body clearance 151 ± 33 ml/min, and renal clearance 110 ± 23 ml/min. No ceftizoxime accumulation was registered during the administration period. Computed multiple-dose values were in good agreement with the measured values, and the pharmacokinetic parameters on the first, fourth and eighth days showed no significant differences. During the study period, the fecal flora displayed a reduction of sensitive gram-negative aerobic bacteria, a slight increase in the amount of enterococci (10⁶ to 10⁸/g feces), and no change in the number ofBacteroides fragilis. Some resistant gram-negative strains increased during the administration period, but most of them could no longer be detected two weeks after administration. Tolerance of ceftizoxime was good in four volunteers. Four other volunteers had gastro-intestinal symptoms and mild fever reactions. One female volunteer was assumed to have an allergic drug reaction. Biochemical, hematological, virological and serological data showed no abnormalities in seven volunteers.