Van Den Anker J N, Van Der Heijden B J, Hop W C, Schoemaker R C, Broerse H M, Neijens H J, De Groot R
Department of Pediatrics, Erasmus University, Rotterdam, The Netherlands.
Pediatr Res. 1995 Nov;38(5):808-11. doi: 10.1203/00006450-199511000-00028.
The multiple-dose pharmacokinetics of ceftazidime (CAZ) (administered twice daily in a 50 mg/kg of body weight i.v. dose) were studied in 10 severely asphyxiated term infants with suspected septicemia on d 3 of life. Nine term infants with suspected septicemia but without asphyxia served as controls. Blood samples were collected from an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after an i.v. bolus injection. A high performance liquid chromatography method was used to determine CAZ concentrations from serum. CAZ pharmacokinetics followed a one-compartment open model. The GFRs of all infants were simultaneously studied by means of the 24-h continuous inulin infusion technique. Elimination serum half-life (5.86 +/- 1.13 h versus 3.85 +/- 0.40 h) and serum trough concentrations (46 +/- 14 mg/L versus 23 +/- 7 mg/L) of CAZ were significantly (p < 0.001) increased in the asphyxiated newborn, whereas total body clearance of CAZ (128.4 +/- 25.1 mL/h versus 205.7 +/- 55.4 mL/h), CAZ clearance per kg (40.9 +/- 6.1 mL/h/kg versus 60.8 +/- 8.3 mL/h/kg), and the GFR expressed in mL/min (3.14 +/- 0.43 versus 4.73 +/- 0.89) were significantly (p < 0.001) decreased in the asphyxiated newborn. We conclude that twice daily administration of 50 mg/kg of body weight CAZ given to asphyxiated term newborns in the first days of life results in significantly higher serum trough levels in comparison with control infants. The impaired CAZ clearance is a result of a significantly decreased GFR.
在出生后第3天，对10名怀疑患有败血症的重度窒息足月儿进行了头孢他啶（CAZ）多剂量药代动力学研究（静脉注射剂量为50mg/kg体重，每日两次）。9名怀疑患有败血症但无窒息的足月儿作为对照。静脉推注后0、0.5、1、2、4、8和12小时从动脉导管采集血样。采用高效液相色谱法测定血清中CAZ浓度。CAZ药代动力学符合一室开放模型。所有婴儿的肾小球滤过率（GFR）通过24小时持续输注菊粉技术同时进行研究。窒息新生儿的CAZ消除血清半衰期（5.86±1.13小时对3.85±0.40小时）和血清谷浓度（46±14mg/L对23±7mg/L）显著升高（p<0.001），而CAZ的总体清除率（128.4±25.1mL/h对205.7±55.4mL/h）、每千克CAZ清除率（40.9±6.1mL/h/kg对60.8±8.3mL/h/kg）以及以mL/min表示的GFR（3.14±0.43对4.73±0.89）在窒息新生儿中显著降低（p<0.001）。我们得出结论，与对照婴儿相比，在出生后第一天给窒息足月儿每日两次给予50mg/kg体重的CAZ会导致血清谷水平显著升高。CAZ清除受损是GFR显著降低的结果。
