用于儿科药物试验的基于生理学的药代动力学建模的监管经验。
Regulatory experience with physiologically based pharmacokinetic modeling for pediatric drug trials.
机构信息
Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
出版信息
Clin Pharmacol Ther. 2012 May;91(5):926-31. doi: 10.1038/clpt.2012.19.
Physiologically based pharmacokinetic (PBPK) approaches that incorporate the developmental physiology and ontogeny of cytochrome P450 (CYP) enzymes may have value in the design of pediatric trials. Four recent submissions to the US Food and Drug Administration (FDA) incorporated different PBPK applications to pediatric drug development.Further testing of PBPK models for three drugs showed that these models generally under predicted drug clearance. PBPK modeling may have potential for improving pediatric trials through the learn-and-confirm approaches utilized in current regulatory submissions.
基于生理学的药代动力学（PBPK）方法，结合细胞色素 P450（CYP）酶的发育生理学和个体发生，在儿科试验设计中可能具有价值。最近向美国食品和药物管理局（FDA）提交的四份文件采用了不同的 PBPK 应用于儿科药物开发。对三种药物的 PBPK 模型进行了进一步测试，结果表明这些模型通常低估了药物清除率。PBPK 模型可能具有通过当前监管提交中使用的学习和确认方法来改善儿科试验的潜力。
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