van den Anker J N, Schoemaker R C, van der Heijden B J, Broerse H M, Neijens H J, de Groot R
Department of Pediatrics, Erasmus University, Rotterdam, The Netherlands.
Antimicrob Agents Chemother. 1995 Sep;39(9):2048-50. doi: 10.1128/AAC.39.9.2048.
Ceftazidime pharmacokinetics in 28 preterm infants (gestational ages, 25.6 to 31.9 weeks) were studied on day 3 of life. Patients with suspected septicemia were randomized on day 1 of life in two groups. One group (n = 13) was administered 25 mg of ceftazidime per kg of body weight once daily, and the other (n = 15) was given 25 mg of ceftazidime per kg twice daily. Both groups also received 25 mg of amoxicillin per kg twice daily. Blood samples were collected on day 3 of life with an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after an intravenous bolus injection. An additional blood sample was taken at 24 h from the group dosed once a day. High-performance liquid chromatography was used to determine serum ceftazidime concentrations. The pharmacokinetics of ceftazidime were best described by using a one-compartment model. The half-life for the elimination of the drug from serum, apparent volume of distribution, total body clearance of ceftazidime, and inulin clearance were not significantly different for both groups. The ceftazidime/inulin clearance ratio was 0.72 for both groups. However, trough concentrations in serum for the twice-daily group were significantly (P < 0.001) higher (42.0 +/- 13.4 mg/liter) than those for the once-daily group (13.1 +/- 4.7 mg/liter). The latter concentrations were all still substantially higher than the MIC of ceftazidime for major neonatal pathogens. We conclude that the currently recommended dosage of 25 mg of ceftazidime per kg twice daily for preterm infants with gestational ages below 32 weeks may be adjusted during the first days of life to one daily dose at 25 mg/kg, provided that for the empirical treatment of septicemia, amoxicillin at 25 mg/kg is also given twice daily.
对28例早产儿（胎龄25.6至31.9周）出生第3天的头孢他啶药代动力学进行了研究。疑似败血症的患者在出生第1天被随机分为两组。一组（n = 13）每天一次给予每千克体重25毫克头孢他啶，另一组（n = 15）每天两次给予每千克体重25毫克头孢他啶。两组还均每天两次给予每千克体重25毫克阿莫西林。在静脉推注后，于出生第3天通过动脉导管在0、0.5、1、2、4、8和12小时采集血样。每天给药一次的组在24小时时额外采集一份血样。采用高效液相色谱法测定血清头孢他啶浓度。头孢他啶的药代动力学用单室模型能得到最佳描述。两组药物从血清中消除的半衰期、表观分布容积、头孢他啶的总体清除率和菊粉清除率均无显著差异。两组的头孢他啶/菊粉清除率均为0.72。然而，每日两次给药组的血清谷浓度（42.0±13.4毫克/升）显著高于每日一次给药组（13.1±4.7毫克/升）（P<0.001）。后者的浓度仍大大高于头孢他啶对主要新生儿病原体的最低抑菌浓度。我们得出结论，对于胎龄低于32周的早产儿，目前推荐的每日两次、每次每千克体重25毫克头孢他啶的剂量在出生后的头几天可调整为每日一次、每千克体重25毫克的剂量，前提是在败血症的经验性治疗中，也每日两次给予每千克体重25毫克阿莫西林。
