Martin E, Koup J R, Paravicini U, Stoeckel K
J Pediatr. 1984 Sep;105(3):475-81. doi: 10.1016/s0022-3476(84)80032-3.
The pharmacokinetics of ceftriaxone was studied in the plasma, urine, and cerebrospinal fluid of seven neonates and seven infants with meningitis. In addition, plasma and urine data were obtained in five neonates and one infant receiving ceftriaxone for other serious infections. All neonates younger than 14 days received daily doses of 50 mg/kg ceftriaxone; all other patients but two received 100 mg/kg. The average weight-corrected values for total body clearance (ClT), volume of distribution (Vdss), and biologic half-life (t 1/2) were 0.37 ml/min/kg, 0.45 L/kg, and 16.2 hours in neonates younger than 1 week; 0.77 ml/min/kg, 0.48 L/kg, and 9.2 hours in neonates older than 1 week; and 1.03 ml/min/kg, 0.39 L/kg, and 7.1 hours in older infants, respectively. There was a significant difference in ClT and t 1/2 between the neonates younger and both neonates older than 1 week, and infants. The Vdss was not significantly different among the three age groups. The average renal clearance in neonates younger than 1 week (0.28 ml/min/kg was 70%, in neonates older than 1 week (0.54 ml/min/kg) was 77%, and in older infants (0.49 ml/min/kg) was 47% of ClT, indicating that nonrenal elimination was less developed in neonates. The quantitation of CSF diffusion of ceftriaxone was assessed by comparison of the areas under the CSF and plasma concentration-time curve. The mean ceftriaxone penetration into the CSF in neonates and infants with bacterial meningitis was 17%. On the other hand, penetration in patients with aseptic meningitis amounted to only 4%. Mean ceftriaxone concentrations in the CSF in patients with bacterial meningitis were 2.8 mg/L after 24 hours, exceeding by many times the minimum inhibitory concentration of the common meningitis pathogens at this time.
在7名患脑膜炎的新生儿和7名婴儿的血浆、尿液和脑脊液中研究了头孢曲松的药代动力学。此外，还获取了5名接受头孢曲松治疗其他严重感染的新生儿和1名婴儿的血浆和尿液数据。所有14日龄以下的新生儿每日接受50mg/kg的头孢曲松剂量；除两名患者外，所有其他患者接受100mg/kg。1周龄以下新生儿的总体清除率（ClT）、分布容积（Vdss）和生物半衰期（t1/2）的平均体重校正值分别为0.37ml/min/kg、0.45L/kg和16.2小时；1周龄以上新生儿分别为0.77ml/min/kg、0.48L/kg和9.2小时；较大婴儿分别为1.03ml/min/kg、0.39L/kg和7.1小时。1周龄以下新生儿与1周龄以上新生儿及婴儿之间的ClT和t1/2存在显著差异。三个年龄组的Vdss无显著差异。1周龄以下新生儿的平均肾清除率（0.28ml/min/kg）占ClT的70%，1周龄以上新生儿（0.54ml/min/kg）占77%，较大婴儿（0.49ml/min/kg）占47%，表明新生儿的非肾清除发育较差。通过比较脑脊液和血浆浓度-时间曲线下的面积来评估头孢曲松在脑脊液中的扩散定量。患细菌性脑膜炎的新生儿和婴儿中，头孢曲松进入脑脊液的平均渗透率为17%。另一方面，无菌性脑膜炎患者的渗透率仅为4%。细菌性脑膜炎患者脑脊液中头孢曲松的平均浓度在24小时后为2.8mg/L，此时超过常见脑膜炎病原体的最低抑菌浓度许多倍。
