Dosing of Ceftriaxone and Metronidazole for Children With Severe Acute Malnutrition.
Dosing of Ceftriaxone and Metronidazole for Children With Severe Acute Malnutrition.
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DOI：
10.1002/cpt.1078
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发表时间：
2018-12
影响因子：
6.7
通讯作者：
FLACSAM-PK Study Group
中科院分区：
文献类型：
--
作者：
Standing JF;Ongas MO;Ogwang C;Kagwanja N;Murunga S;Mwaringa S;Ali R;Mturi N;Timbwa M;Manyasi C;Mwalekwa L;Bandika VL;Ogutu B;Waichungo J;Kipper K;Berkley JA;FLACSAM-PK Study Group
患有严重急性营养不良（SAM）的婴幼儿可使用经验性广谱抗菌素治疗。头孢曲松是目前治疗侵袭性感染的二线药物。口服甲硝唑主要针对小肠细菌过度生长。患有SAM的儿童可能会改变药物的吸收、分布、代谢和消除。研究头孢曲松和甲硝唑的群体药代动力学，以推荐最佳剂量。81例SAM患者（年龄2-45个月）提供了234份总头孢曲松、甲硝唑和羟甲硝唑的给药后药代动力学样本。在其中190个样本中也检测了头孢曲松蛋白结合。三室模型充分描述了游离头孢曲松，Michaelis-Menten模型用于浓度和白蛋白依赖性蛋白结合。对甲硝唑和羟甲硝唑均采用单室模型，预测在第一次通过过程中只有1%的羟甲硝唑形成。模拟显示，80 mg/kg每日一次的头孢曲松和12.5 mg/kg每日两次的甲硝唑足以达到治疗目标。
Infants and young children with severe acute malnutrition (SAM) are treated with empiric broad‐spectrum antimicrobials. Parenteral ceftriaxone is currently a second‐line agent for invasive infection. Oral metronidazole principally targets small intestinal bacterial overgrowth. Children with SAM may have altered drug absorption, distribution, metabolism, and elimination. Population pharmacokinetics of ceftriaxone and metronidazole were studied, with the aim of recommending optimal dosing. Eighty‐one patients with SAM (aged 2–45 months) provided 234 postdose pharmacokinetic samples for total ceftriaxone, metronidazole, and hydroxymetronidazole. Ceftriaxone protein binding was also measured in 190 of these samples. A three‐compartment model adequately described free ceftriaxone, with a Michaelis–Menten model for concentration and albumin‐dependent protein binding. A one‐compartment model was used for both metronidazole and hydroxymetronidazole, with only 1% of hydroxymetronidazole predicted to be formed during first‐pass. Simulations showed 80 mg/kg once daily of ceftriaxone and 12.5 mg/kg twice daily of metronidazole were sufficient to reach therapeutic targets.
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影响因子：
6.1
作者：
Lindbom, L;Pihlgren, P;Jonsson, N
通讯作者：
Jonsson, N
影响因子：
3.4
作者：
Schleibinger, Michael;Steinbach, Catherine L.;Kees, Martin G.
通讯作者：
Kees, Martin G.
影响因子：
5.2
作者：
De Cock, R. F. W.;Smits, A.;Knibbe, C. A. J.
通讯作者：
Knibbe, C. A. J.
影响因子：
4.9
作者：
Agudelo, M.;Vesga, O.
通讯作者：
Vesga, O.
影响因子：
4.5
作者：
Savic, Radojka M.;Karlsson, Mats O.
通讯作者：
Karlsson, Mats O.