Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children.
Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children.
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DOI：
10.1002/jcph.1116
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发表时间：
2018-08
影响因子：
2.9
通讯作者：
Pediatric Trial Network Steering Committee
中科院分区：
文献类型：
--
作者：
Hornik CP;Gonzalez D;van den Anker J;Atz AM;Yogev R;Poindexter BB;Ng KC;Delmore P;Harper BL;Melloni C;Lewandowski A;Gelber C;Cohen-Wolkowiez M;Lee JH;Pediatric Trial Network Steering Committee
氯胺酮是一种N-甲基-D-天冬氨酸受体拮抗剂，标签外使用，以促进接受侵入性手术的儿童的分离麻醉。氯胺酮可用于静脉内和肌内给药，通常用于血管通路受限时。儿童的药代动力学（PK）数据很少，儿童肌内注射氯胺酮的生物利用度未知。我们在接受肌肉注射或静脉注射氯胺酮的儿童中进行了2项氯胺酮的前瞻性PK研究，并使用非线性混合效应方法合并数据以开发儿科群体PK模型。我们通过进行给药模拟来应用我们的模型，所述给药模拟靶向先前与镇痛（>100 ng/mL）和麻醉唤醒（750 ng/mL）相关的血浆浓度。共有113名儿童（50名肌肉注射氯胺酮和63名静脉注射氯胺酮），中位年龄为3.3岁（范围：0.02 - 17.6岁），中位体重为14 kg（2.4 - 176.1），提供了275份血浆样本（肌肉注射氯胺酮后149份，静脉注射氯胺酮后126份）。肌内给药后一级吸收和一级消除的二室模型最好地描述了数据。在中心和外周分布容积（指数1）以及清除率和房室间清除率（指数0.75）的基础模型中纳入了异速生长比例权重。模型估计的肌肉注射氯胺酮的生物利用度为41%。给药模拟表明，根据年龄，2 mg/kg静脉给药和8 mg/kg或6 mg/kg肌内给药可为持续长达20分钟的手术提供足够的镇静（血浆氯胺酮浓度>750 ng/mL）。
Ketamine is an N-methyl D-aspartate receptor antagonist used off label to facilitate dissociative anesthesia in children undergoing invasive procedures. Available for both intravenous and intramuscular administration, ketamine is commonly used when vascular access is limited. Pharmacokinetic (PK) data in children are sparse, and the bioavailability of intramuscular ketamine in children is unknown. We performed 2 prospective PK studies of ketamine in children receiving either intramuscular or intravenous ketamine, and combined the data to develop a pediatric population PK model using nonlinear mixed effects methods. We applied our model by performing dosing simulations targeting plasma concentrations previously associated with analgesia (>100 ng/mL) and anesthesia awakening (750 ng/mL). A total of 113 children (50 intramuscular and 63 intravenous ketamine) with a median age of 3.3 years (range: 0.02 to 17.6 years), and median weight of 14 kg (2.4 to 176.1) contributed 275 plasma samples (149 after intramuscular, 126 after intravenous ketamine). A 2-compartment model with first-order absorption following intramuscular administration and first-order elimination described the data best. Allometrically scaled weight was included in the base model for central and peripheral volume of distribution (exponent 1), and for clearance and intercompartmental clearance (exponent 0.75). Model estimated bioavailability of intramuscular ketamine was 41%. Dosing simulations suggest that doses of 2 mg/kg intravenously and 8mg/kg or 6 mg/kg intramuscularly depending on age provide adequate sedation (plasma ketamine concentrations >750 ng/mL) for procedures lasting up to 20 minutes.
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影响因子：
2.5
作者：
Jelliffe, RW;Gomis, P;Sattler, FR
通讯作者：
Sattler, FR
影响因子：
3.3
作者：
Björkman, S;Redke, F
通讯作者：
Redke, F
影响因子：
2.6
作者：
Keizer, Ron J;Jansen, Robert S;Rosing, Hilde;Thijssen, Bas;Beijnen, Jos H;Schellens, Jan H M;Huitema, Alwin D R
通讯作者：
Huitema, Alwin D R
影响因子：
9.8
作者：
IDVALL, J;AHLGREN, I;STENBERG, P
通讯作者：
STENBERG, P
影响因子：
6.1
作者：
Keizer, Ron J.;van Benten, Michel;Huitema, Alwin D. R.
通讯作者：
Huitema, Alwin D. R.