Zhang Huanian, Wang Yang, Gao Ping, Hu Jiasheng, Chen Yujun, Zhang Long, Shen Xiantao, Xu Hua, Xu Qiong
Department of Clinical Pharmacology, Wuhan Children's Hospital, Hubei, China.
Department of Pediatric Neurology, Wuhan Children's Hospital, Hubei, China.
J Clin Pharmacol. 2016 Jun;56(6):740-8. doi: 10.1002/jcph.653. Epub 2015 Dec 21.
Although vancomycin pharmacokinetics are affected by age and renal function in adults and older children, its pharmacokinetics in children aged 1 month to 2 years remained unclear. We investigated clinical outcome and nephrotoxicity in younger children with renal insufficiency who were treated with vancomycin. One hundred and ten children aged 1 month to 2 years were enrolled, and they were divided into 3 groups: normal renal function (group A), mild renal insufficiency (group B), and moderate renal insufficiency (group C). A population pharmacokinetic model was established. Significant differences were observed for trough concentration, AUC0-24 h , CL, and t1/2 in the 3 groups. When given at 40 mg/kg per day, 36.4%, 62.5%, and 85.0% of children achieved the target of AUC/MIC ≥ 400, and 47.0%, 70.8%, and 95% of children obtained early good clinical outcomes in groups A, B, and C (P < .05), respectively. One child in group A and 4 children in group C suffered from acute kidney injury. These results indicated that children with renal insufficiency readily achieved the target AUC/MIC but were at increased risk of nephrotoxicity. Vancomycin clearance and creatinine clearance were not correlated with each other in children with renal insufficiency, indicating that both renal function and serum concentration should be monitored during vancomycin therapy.
尽管万古霉素的药代动力学在成人和大龄儿童中受年龄和肾功能影响，但其在1个月至2岁儿童中的药代动力学仍不清楚。我们调查了接受万古霉素治疗的肾功能不全幼儿的临床结局和肾毒性。纳入110名1个月至2岁的儿童，并将他们分为3组：肾功能正常（A组）、轻度肾功能不全（B组）和中度肾功能不全（C组）。建立了群体药代动力学模型。3组在谷浓度、AUC0-24 h、CL和t1/2方面观察到显著差异。当每天给予40 mg/kg时，A组、B组和C组分别有36.4%、62.5%和85.0%的儿童达到AUC/MIC≥400的目标，分别有47.0%、70.8%和95%的儿童获得早期良好临床结局（P<0.05）。A组有1名儿童和C组有4名儿童发生急性肾损伤。这些结果表明，肾功能不全的儿童容易达到目标AUC/MIC，但肾毒性风险增加。在肾功能不全的儿童中，万古霉素清除率和肌酐清除率彼此不相关，这表明在万古霉素治疗期间应同时监测肾功能和血清浓度。
