Comparative Pharmacokinetics andSerumBactericidal Activities ofSCE-2787 andCeftazidime

serumbactericidal activities, andside effects wereinvestigated inarandomized crossover study. Atotal of12healthy volunteers received a20-min infusion of1.5gofSCE-2787 or2.0gofceftazidime. Serumandurineconcentrations weredetermined bythebioassay methodandbyhigh-pressure liquid chromatography (HPLC). Themean(±standard deviation) drugconcentrations inserumattheendofinfusion ofSCE-2787 andceftazidime were124.4 + 23.8and233.1 ± 54.1mg/liter, respectively. Theurine recovery ofSCE-2787 was87.8%± 5.5%ofdosein24handforceftazidime was85.8%± 6.3%ofdosein24h. Metabolites ofSCE-2787 could notbedetected byHPLCinserumorurine. Pharmacokinetic parameters were calculated bothwithanoncompartmental analysis andonthebasis ofanopentwo-compartment model(drugs areadministered into andeliminated fromacentral compartment only. However, reversible drugdistribution fromthecentral space occurs simultaneously into oneperipheral space). Theareaundertheconcentration time curvefrom0htoinfinity ofSCE-2787 was197.9 ±25.4mg.h/liter, andthat ofceftazidime was334.2 + 40.0 mg-h/liter. SCE-2787 hadameanterminal half-life intheelimination phaseof109.0 ± 15.3min,while that ofceftazidime was99.0± 13.4min.Thevolume ofdistribution atsteady state ofSCE-2787 was17.1+ 1.6 liters/70 kg,andthatofceftazidime was12.2± 1.3liters/70 kg.Themeanresidence timeofSCE-2787 was 136.4 + 15.4min,andthat ofceftazidime was122.9 ± 12.7min.Therenal clearance per1.73m2ofSCE-2787 was103.1 ± 12.3mWmin, andthatofceftazidime was80.6± 13.2ml/min. Theserumbactericidal activities weremeasured withthemicrodilution methodofStratton andReller (L.B.Reller andC.W. Stratton, J. Infect. Dis.136:196-204, 1977)against 40clinically isolated strains. Onehourafter administration, we measured meanreciprocal bactericidal titers ofSCE-2787 andceftazidime, respectively, against Escherichia coli of388and243,against KiebsieUla pneumoniae of395and138, against Pseudomonas aeruginosa of13.0 and 12.7, andagainst Staphylococcus aureus of32.2and4.0. Nosevere side effects wereobserved inthis single drug administration.