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Pharmacokinetic and pharmacodynamic considerations of general anesthesia in pediatric subjects
Expert Opinion on Drug Metabolism & Toxicology ( IF 3.9 ) Pub Date : 2020-03-17 , DOI: 10.1080/17425255.2020.1739648
Brian J Anderson 1 , James D Morse 2 , Jacqueline A Hannam 2 , L Ignacio Cortinez 3
Affiliation  

ABSTRACT Introduction: The target concentration strategy uses PKPD information for dose determination. Models have also quantified exposure-response relationships, improved understanding of developmental pharmacokinetics, rationalized dose prescription, provided insight into the importance of covariate information, explained drug interactions and driven decision-making and learning during drug development. Areas covered: The prime PKPD consideration is parameter estimation and quantification of variability. The main sources of variability in children are age (maturation) and weight (size). Model use is mostly confined to pharmacokinetics, partly because anesthesia effect models in the young are imprecise. Exploration of PK and PD covariates and their variability hold potential to better individualize treatment. Expert opinion: The ability to model drugs using computer-based technology is hindered because covariate data required to individualize treatment using these programs remain lacking. Target concentration intervention strategies remain incomplete because covariate information that might better predict individualization of dose is absent. Pharmacogenomics appear a valuable area for investigation for pharmacodynamics and pharmacodynamics. Effect measures in the very young are imprecise. Assessment of the analgesic component of anesthesia is crude. While neuromuscular monitoring is satisfactory, depth of anaesthesia EEG interpretation is inadequate. Closed loop anesthesia is possible with better understanding of EEG changes.

中文翻译:

儿科全身麻醉的药代动力学和药效学考虑

摘要 介绍:目标浓度策略使用 PKPD 信息进行剂量确定。模型还量化了暴露-反应关系,提高了对发育药代动力学的理解,合理化了剂量处方,提供了对协变量信息重要性的洞察,解释了药物相互作用并推动了药物开发过程中的决策和学习。涵盖的领域: PKPD 的主要考虑因素是参数估计和可变性的量化。儿童变异的主要来源是年龄(成熟)和体重(大小)。模型的使用主要限于药代动力学,部分原因是年轻人的麻醉效应模型不精确。对 PK 和 PD 协变量及其变异性的探索具有更好地个体化治疗的潜力。专家意见:使用基于计算机的技术对药物进行建模的能力受到阻碍,因为仍然缺乏使用这些程序进行个性化治疗所需的协变量数据。目标浓度干预策略仍然不完整,因为缺少可能更好地预测剂量个体化的协变量信息。药物基因组学似乎是药效学和药效学研究的一个有价值的领域。对非常年轻的影响措施是不精确的。对麻醉镇痛成分的评估是粗略的。虽然神经肌肉监测令人满意,但麻醉深度脑电图解释不充分。通过更好地了解 EEG 变化,可以进行闭环麻醉。目标浓度干预策略仍然不完整,因为缺少可能更好地预测剂量个体化的协变量信息。药物基因组学似乎是药效学和药效学研究的一个有价值的领域。对非常年轻的影响措施是不精确的。对麻醉镇痛成分的评估是粗略的。虽然神经肌肉监测令人满意,但麻醉深度脑电图解释不充分。通过更好地了解 EEG 变化,可以进行闭环麻醉。目标浓度干预策略仍然不完整,因为缺少可能更好地预测剂量个体化的协变量信息。药物基因组学似乎是药效学和药效学研究的一个有价值的领域。对非常年轻的影响措施是不精确的。对麻醉镇痛成分的评估是粗略的。虽然神经肌肉监测令人满意,但麻醉深度脑电图解释不充分。通过更好地了解 EEG 变化,可以进行闭环麻醉。对麻醉镇痛成分的评估是粗略的。虽然神经肌肉监测令人满意,但麻醉深度脑电图解释不充分。通过更好地了解 EEG 变化,可以进行闭环麻醉。对麻醉镇痛成分的评估是粗略的。虽然神经肌肉监测令人满意,但麻醉深度脑电图解释不充分。通过更好地了解 EEG 变化,可以进行闭环麻醉。
更新日期:2020-03-17
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