Plasma and epithelial lining fluid pharmacokinetics of ceftolozane and tazobactam alone and in combination in mice

摘要: Ceftolozane is a new cephalosporin with activity against Gram-negative and Gram-positive microorganisms. However, the compound susceptible to degradation by extended-spectrum beta-lactamases (ESBLs). Tazobactam an ESBL inhibitor combined ceftolozane broaden its activity. Surprisingly, although tazobactam has been available for over 20 years, few if any reliable data exist on pharmacokinetic (PK) properties in mice. To evaluate PK pharmacodynamic (PD) relationships mice, of were extensively investigated. Thigh-infected neutropenic CD-1 mice injected intraperitoneally single 0.1-ml dose containing ceftolozane, tazobactam, or both compounds. was applied 2-fold-increasing doses 4 mg/kg body weight 64 alone combination. reverse (thus, 64/4 mg/kg, 32/8 etc.) (n = 2 per time point). In separate validation experiments, ceftolozane-tazobactam given combination at 8/32 Plasma samples (one mouse) bronchoalveolar lavage collected up 12 points until 6 h after administration. There no significant differences versus combined, indicating interaction. The PKs linear proportional compounds showed good penetration epithelial lining fluid. estimated mean (standard deviation) half-life 0.287 (0.031 h), that 0.176 (0.026), V 0.43 liter/kg 1.14 liter/kg, respectively. estimates parameters can also be used (re)interpret PD data.