摘要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.