定量药理学与儿童药物研发和合理用药

1引言儿童合理用药是摆在世界各国临床药理学工作者和儿科医生面前一个亟待解决而又悬而难决的课题。长期以来,儿童作为弱势群体和人类的未来是社会大众的保护对象,伦理上不接受儿童作为药物试验的受试者。即使是常用于儿童的药物,也很少在儿童中试验过。

Pharmacometrics in pediatric drug development and rational dosage

This article provides a comprehensive overview of key issues related to pediatric drug development and rational dosing guidance in pediatrics with an emphasis on how pharmacometrics can improve the efficiency and productivity of pediatric trials.The pharmacokinetics (PK)and pharmacodynamics(PD)of drugs are often different between adult and pediatric populations which necessitate specific studies in children.The aims of this review are to discuss a number of recent methodological developments of modeling and simulation that facilitate the evaluation of drugs in pediatrics.Specific focus has been placed on addressing the key issues of PK/PD scaling,sparse sampling,colinearity,covariate evaluation,dose optimization for trial design and label,modeling strategies and validation approaches.The feat ures and potential advantages of Bayesian hierarchical model,physiology-based PK models,and K-PD models are also presented.