Ontogeny of Drug-Metabolizing Enzymes.
Ontogeny of Drug-Metabolizing Enzymes.
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DOI：
10.1007/978-1-0716-1554-6_18
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发表时间：
2021
影响因子：
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通讯作者：
Aarzoo Thakur;M. Parvez;J. Leeder;B. Prasad
中科院分区：
文献类型：
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作者：
Aarzoo Thakur;M. Parvez;J. Leeder;B. Prasad
近50%的处方药缺乏适合年龄的剂量指南，因此被“标签外”使用。只有约10%的新生儿和婴儿处方药的安全性或有效性进行了研究。儿童药物代谢的不成熟往往与药物毒性有关。本章总结了参与药物氧化、还原、水解和结合的主要人体代谢酶的个体发育数据。个体药物代谢酶的个体发育数据对于准确预测药物在儿童体内的药代动力学和毒性具有重要意义。这些信息对于设计临床研究以适当地测试药理学假设和开发更安全的儿科药物，以及取代体重或表面积标准化药物给药的长期实践至关重要。个体发育数据的应用生理基础上的药代动力学模型和监管提交进行了讨论。
Almost 50% of prescription drugs lack age-appropriate dosing guidelines and therefore are used “off-label.” Only ~10% drugs prescribed to neonates and infants have been studied for safety or efficacy. Immaturity of drug metabolism in children is often associated with drug toxicity. This chapter summarizes data on the ontogeny of major human metabolizing enzymes involved in oxidation, reduction, hydrolysis, and conjugation of drugs. The ontogeny data of individual drug-metabolizing enzymes are important for accurate prediction of drug pharmacokinetics and toxicity in children. This information is critical for designing clinical studies to appropriately test pharmacological hypotheses and develop safer pediatric drugs, and to replace the long-standing practice of body weight- or surface area-normalized drug dosing. The application of ontogeny data in physiologically based pharmacokinetic model and regulatory submission are discussed.