Nicolau David P, Sutherland Christina A, Arguedas Adriano, Dagan Ron, Pichichero Micheal E
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut 06102-5037, USA.
Paediatr Drugs. 2007;9(2):119-23. doi: 10.2165/00148581-200709020-00005.
Despite the wide-scale use of cefprozil for acute otitis media (AOM), there are only limited data available regarding the pharmacokinetic profile of this agent in the pediatric population.
To characterize the plasma and middle ear fluid (MEF) pharmacokinetic profile of cefprozil in pediatric patients with AOM.
Pharmacokinetic sampling was obtained as part of a phase IV, multicenter, open-label study of children with AOM receiving cefprozil suspension 15 mg/kg twice daily. A single blood sample was obtained 4-6 days after the initiation of cefprozil therapy and a simultaneous MEF sample was obtained by tympanocentesis when clinically indicated. Cefprozil concentrations in both matrices were determined using a validated high-performance liquid chromatography methodology. A composite profile of cefprozil concentration data in each matrix was constructed and values for the pharmacokinetic parameters were obtained using conventional modeling techniques.
Plasma concentrations were obtained in 53 children aged 6-48 months. In this population the maximum concentration (C(max)) in plasma was 9.18 microg/mL, the time to C(max) (t(max)) was 1.5 hours, and the terminal elimination half-life (t((1/2))(beta)) was 0.98 hours. Simultaneous plasma and MEF concentration data were available in 22 children. In this subset the C(max) in plasma was 8.2 microg/mL, the t(max) was 1.9 hours, and the t((1/2))(beta) was 1.02 hours; the corresponding MEF C(max) was 2.4 microg/mL, the t(max) was 3.5 hours, and the t((1/2))(beta) was 1.23 hours. Cefprozil MEF penetration as assessed using the ratio of the area under the concentration-time curves from the two matrices was 28%. Moreover, concentrations in MEF approximated 1 microg/mL 6 hours' post-dose.
The plasma profile of cefprozil in the current analysis is consistent with previously reported values in children receiving the 15 mg/kg twice daily dose. MEF penetration and the duration of drug exposure at the site of infection support the clinical utility of this agent for organisms with minimum inhibitory concentrations (MIC) of < or =1 microg/mL. However, these results also predict higher clinical failure when using this dose of cefprozil against penicillin-non-susceptible Streptococcus pneumoniae or Haemophilus influenzae because of typically higher MIC values for these organisms.
尽管头孢丙烯已广泛用于治疗急性中耳炎（AOM），但关于该药物在儿科人群中的药代动力学资料有限。
描述头孢丙烯在患AOM的儿科患者中的血浆和中耳液药代动力学特征。
药代动力学采样是一项IV期、多中心、开放标签研究的一部分，该研究纳入接受每日两次15mg/kg头孢丙烯混悬液治疗的AOM患儿。在开始头孢丙烯治疗4 - 6天后采集一份血样，临床指征明确时通过鼓膜穿刺术同时采集一份中耳液样本。使用经过验证的高效液相色谱法测定两种基质中的头孢丙烯浓度。构建每种基质中头孢丙烯浓度数据的综合概况，并使用传统建模技术获得药代动力学参数值。
在53名6 - 48个月大的儿童中获得了血浆浓度数据。该人群血浆中的最大浓度（C(max)）为9.18μg/mL，达峰时间（t(max)）为1.5小时，终末消除半衰期（t((1/2))(β)）为0.98小时。22名儿童同时获得了血浆和中耳液浓度数据。在这个亚组中，血浆C(max)为8.2μg/mL，t(max)为1.9小时，t((1/2))(β)为1.02小时；相应的中耳液C(max)为2.4μg/mL，t(max)为3.5小时，t((1/2))(β)为1.23小时。使用两种基质浓度 - 时间曲线下面积之比评估的头孢丙烯中耳液渗透率为28%。此外，给药6小时后中耳液浓度约为1μg/mL。
本次分析中头孢丙烯的血浆概况与先前报道的接受每日两次15mg/kg剂量的儿童中的值一致。中耳液渗透以及感染部位的药物暴露持续时间支持该药物对最低抑菌浓度（MIC）≤1μg/mL的微生物的临床效用。然而，这些结果也预测，使用该剂量的头孢丙烯治疗对青霉素不敏感的肺炎链球菌或流感嗜血杆菌时临床失败率会更高，因为这些微生物的MIC值通常更高。
