COMPARATIVE PHARMACOKINETICS AND SERUM BACTERICIDAL ACTIVITIES OF SCE-2787 AND CEFTAZIDIME

Ceftazidime and the new SCE-2787 are parenteral cephalosporins with a broad antimicrobial spectrum. Pharmacokinetics, serum bactericidal act ivities, and side effects were investigated in a randomized crossover study. A total of 12 healthy volunteers received a 20-min infusion of 1.5 g of SCE-2787 or 2.0 g of ceftazidime. Serum and urine concentrati ons were determined by the bioassay method and by high-pressure liquid chromatography (HPLC). The mean (+/- standard deviation) drug concent rations in serum at the end of infusion of SCE-2787 and ceftazidime we re 124.4 +/- 23.8 and 233.1 +/- 54.1 mg/liter, respectively. The urine recovery of SCE-2787 was 87.8% +/- 5.5% of dose in 24 h and for cefta zidime was 85.8% +/- 6.3% of dose in 24 h. Metabolites of SCE-2787 cou ld not be detected by HPLC in serum or urine. Pharmacokinetic paramete rs were calculated both with a noncompartmental analysis and on the ba sis of an open two-compartment model (drugs are administered into and eliminated from a central compartment only. However, reversible drug d istribution from the central space occurs simultaneously into one peri pheral space). The area under the concentration time curve from 0 h to infinity of SCE-2787 was 197.9 +/- 25.4 mg . h/liter, and that of cef tazidime was 334.2 +/- 40.0 mg . h/liter. SCE-2787 had a mean terminal half-life in the elimination phase of 109.0 +/- 15.3 min, while that of ceftazidime was 99.0 +/- 13.4 min. The volume of distribution at st eady state of SCE-2787 was 17.1 +/- 1.6 liters/70 kg, and that of ceft azidime was 12.2 +/- 1.3 liters/70 kg. The mean residence time of SCE- 2787 was 136.4 +/- 15.4 min, and that of ceftazidime was 122.9 +/- 12. 7 min. The renal clearance per 1.73 m2 of SCE-2787 was 103.1 +/- 12.3 ml/min, and that of ceftazidime was 80.6 +/- 13.2 ml/min. The serum ba ctericidal activities were measured with the microdilution method of S tratton and Reller (L. B. Reller and C. W. Stratton, J. Infect. Dis. 1 36:196-204, 1977) against 40 clinically isolated strains. One hour aft er administration, we measured mean reciprocal bactericidal titers of SCE-2787 and ceftazidime, respectively, against Escherichia coli of 38 8 and 243, against Klebsiella pneumoniae of 395 and 138, against Pseud omonas aeruginosa of 13.0 and 12.7, and against Staphylococcus aureus of 32.2 and 4.0. No severe side effects were observed in this single d rug administration.