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首页> 外文期刊>Pediatric critical care medicine: a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies >Prediction and Comparison of Fentanyl Infusion Pharmacokinetics in Obese and Nonobese Children
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Prediction and Comparison of Fentanyl Infusion Pharmacokinetics in Obese and Nonobese Children

机译：芬太尼输液药代动力学在肥胖和非同源儿童中的预测与比较

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Objectives: To compare fentanyl infusion pharmacokinetic variables in obese children and nonobese children. Design: A pharmacokinetic simulation study. Setting: We used a semi-physiologically based pharmacokinetic model to generate fentanyl pharmacokinetic variables. Subjects: Simulations of pharmacokinetic variables were based on historical inpatient demographic data in less than 18-year-olds. Interventions: Obese children were defined as children less than 2 years with weight-for-length greater than or equal to 97.7th percentile or body mass index-for-age greater than or equal to 95th percentile for greater than or equal to 2-17-year-olds. Measurements and Main Results: Overall, 4,376 patients were included, with 807 (18.4%) classified as obese children. The majority (52.9%) were male, with a median age of 8.1 years (interquartile range, 4.3-13.0 yr). The differences in total clearance (CLS), volume of distribution at steady-state values, weight-normalized CLS, and weight-normalized volume of distribution at steady state were assessed in obese children and nonobese children. Multivariable analyses indicated that obesity was significantly associated with a higher CLS in obese children greater than 6-year-olds (p < 0.0375). However, there was an 11-30% decrease in weight-normalized CLS in obese children versus nonobese children in all age groups (p < 0.05). Both volume of distribution at steady state and weight-normalized volume of distribution at steady state increased significantly in obese children compared with nonobese children (p < 0.05). Fentanyl plasma concentration-time profiles of obese children and nonobese children pairs (ages 4, 9, and 15) receiving 1 mu g/kg/hr using total body weight were also compared. Steady-state concentrations of the obese children using similar weight-based dosing increased by 25%, 77%, and 44% in comparison to nonobese children 4-, 9-, and 15-year-olds, respectively. Time to steady state and elimination half-lives were two- to four-fold longer in obese children. An additional simulation was conducted for 15-year-old obese children and nonobese children using a fixed dose of 50 mu g/hr and it provided similar pharmacokinetic profiles. Conclusions: CLS may increase less than proportional to weight in obese children greater than 6-year-olds, while volume of distribution at steady state increases more than proportional to weight in all obese children compared with nonobese children. Weight-based dosing in obese children may cause an increase in steady-state concentration while prolonging the time to steady state. Exploring alternative dosing strategies for obese children is warranted.
机译：目的：比较福尼斯灌注药代动力学变量在肥胖儿童和非同源儿童中。设计：药代动力学模拟研究。设置：我们使用了基于半生物学上的药代动力学模型来产生芬太尼药代动力学变量。主题：药代动力学变量的模拟基于少于18岁的历史住院人口统计数据。干预措施：肥胖儿童被定义为少于或等于97.7百分位或体重指数的小于或等于95百分位大于或等于2-17的儿童 - 年龄。测量和主要结果：总体而言，4,376名患者包括在内，807名（18.4％）归类为肥胖儿童。大多数（52.9％）是男性，中位年龄为8.1年（四分位数范围，4.3-13.0 YR）。在肥胖儿童和非稳定状态下，评估了稳态值，稳态值，体积归一化Cls和稳态分布的重量标准化分布体积的差异。多变量分析表明，肥胖与大于6岁儿童的肥胖儿童中的肥胖显着相关（P <0.0375）。然而，肥胖儿童的重量标准化CLS减少11-30％，而所有年龄组的非同源儿童（P <0.05）。与非同源儿童相比，肥胖儿童在稳定状态下，稳态稳态和重量标准化分布的稳态和重量标准化的分布量显着增加（P <0.05）。还比较了使用总体重量接受1μg/ kg / hr的肥胖儿童和非同源儿童对（4,9和15岁）的芬太尼血浆浓度 - 时间谱。与非同意儿童4-，9-和15岁儿童相比，使用类似的基于体重的剂量的肥胖儿童的稳态浓度增加25％，77％和44％。肥胖儿童的稳定状态和消除半衰期的时间是两到四倍。使用固定剂量为50μg/ hr，为15岁的肥胖儿童和非同源儿童进行了额外的模拟，并提供了类似的药代动力学谱。结论：CLS可能增加肥胖儿童大于6岁儿童的重量比例，而稳态分布的分布量比非同源儿童相比，所有肥胖儿童的重量比成比例增加。肥胖儿童中的重量给药可能导致稳态浓度的增加，同时延长稳定状态。有必要探索肥胖儿童的替代给药策略。

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