药代动力学期末复习-定量药理学研究进展.ppt

Example of PK/PD in Phase 2~3 R. Lalonade Company Logo Pharmacometrics 生物药剂学 药物动力学 群体药物动力学 药动学/药效学 模型化/仿真 定量药理学核心学科 Add Your Text 模型化与仿真 (Modeling and Simulation，MS) 模型化：根据科学假设针对数据建立模型 仿真：根据已有的模型模拟可能的数据 实践 理论 实践 …… Data Model Modeling Simulation 学习/理解 确认 再学习/再理解 （数据） （模型） （新数据） * The Role of PKPD MS in Phase 2~3 Learning Confirming Phase IIb Phase III Toleration Human PK-PD Efficacy and Safety Dose/Exposure-Response Dose Adjustments Therapeutic Index Covariate Effects Phase I Phase IIa Pre-Clinical Efficacy Toxicology PK-PD Registration Labeling Dosage Phase IV Results Relative to Competitors, Regional Differences, Therapeutic Index Continuum of Learn/Confirm/Predict at Each Decision Point. MS MS MS MS MS Confidence in Drug Disease Model Uncertainty Lalonde RL et al., Model-based drug development. Clinical Pharmacology Therapeutics 2007;82:21-32 “indication” level Pre-Clinical FIH FIP POC P3 Registration P4 “mechanism” level “compound” level Relative Data Contribution to Models 3) Study Design = OCs Trial Conduct 2) Decision Criteria = 1) Define Questions Relevant Data Volume to Models PTS 4) Update models R. Lalonade P. Milligan The Role of PKPD MS in Phase 2~3 Learning Confirming 定量药理学研究展望 药物动力学 - 群体药物动力学 传统房室模型 - 基于解剖生理/作用机制的生理学模型 药物动力学 - 药物动力学/药效动力学 药物动力学/药效动力学 - 基于机制的药物动力学/药效动力学 群体药物动力学和药物动力学/药效动力学 被动表述 - 主动参与，主动干预 ?临床药学/治疗药物监测 ?新药研制的各期的模型化与仿真 PopPK, PK/PD– an uphill climb … … PopPK, PK/PD– but nice view! * * * * * * * As a compound moves through from Pre-clinical through to Phase 4 and LOE (loss of exclusivity) the ratio of information available to teams of on the compound, mechanism, and indication levels will change. Earlier on we have little information on the particular compound (which will be addressed over time). Therefore, in order to make most effective use of the sparse compound level data, teams should to leverage in a more