Schuck Edgar, Bohnert Tonika, Chakravarty Arijit, Damian-Iordache Valeriu, Gibson Christopher, Hsu Cheng-Pang, Heimbach Tycho, Krishnatry Anu Shilpa, Liederer Bianca M, Lin Jing, Maurer Tristan, Mettetal Jerome T, Mudra Daniel R, Nijsen Marjoleen Jma, Raybon Joseph, Schroeder Patricia, Schuck Virna, Suryawanshi Satyendra, Su Yaming, Trapa Patrick, Tsai Alice, Vakilynejad Majid, Wang Shining, Wong Harvey
Modeling and Simulation, Eisai Inc., 155 Tice Blvd, Woodcliff Lake, NJ, 07677, USA,
AAPS J. 2015 Mar;17(2):462-73. doi: 10.1208/s12248-014-9716-2. Epub 2015 Jan 29.
The application of modeling and simulation techniques is increasingly common in preclinical stages of the drug discovery and development process. A survey focusing on preclinical pharmacokinetic/pharmacodynamics (PK/PD) analysis was conducted across pharmaceutical companies that are members of the International Consortium for Quality and Innovation in Pharmaceutical Development. Based on survey responses, 68% of companies use preclinical PK/PD analysis in all therapeutic areas indicating its broad application. An important goal of preclinical PK/PD analysis in all pharmaceutical companies is for the selection/optimization of doses and/or dose regimens, including prediction of human efficacious doses. Oncology was the therapeutic area with the most PK/PD analysis support and where it showed the most impact. Consistent use of more complex systems pharmacology models and hybrid physiologically based pharmacokinetic models with PK/PD components was less common compared to traditional PK/PD models. Preclinical PK/PD analysis is increasingly being included in regulatory submissions with ~73% of companies including these data to some degree. Most companies (86%) have seen impact of preclinical PK/PD analyses in drug development. Finally, ~59% of pharmaceutical companies have plans to expand their PK/PD modeling groups over the next 2 years indicating continued growth. The growth of preclinical PK/PD modeling groups in pharmaceutical industry is necessary to establish required resources and skills to further expand use of preclinical PK/PD modeling in a meaningful and impactful manner.
建模与模拟技术在药物发现与开发过程的临床前阶段应用日益普遍。针对制药开发质量与创新国际联盟成员的制药公司开展了一项聚焦临床前药代动力学/药效学（PK/PD）分析的调查。根据调查反馈，约68%的公司在所有治疗领域使用临床前PK/PD分析，表明其应用广泛。所有制药公司临床前PK/PD分析的一个重要目标是用于剂量和/或给药方案的选择/优化，包括预测人体有效剂量。肿瘤学是获得PK/PD分析支持最多且显示出最大影响的治疗领域。与传统PK/PD模型相比，更复杂的系统药理学模型以及带有PK/PD组件的混合生理药代动力学模型的持续使用并不常见。临床前PK/PD分析越来越多地被纳入监管申报资料，约73%的公司在一定程度上包含了这些数据。大多数公司（约86%）已看到临床前PK/PD分析对药物开发的影响。最后，约59%的制药公司计划在未来两年扩大其PK/PD建模团队，表明其持续增长。制药行业临床前PK/PD建模团队的增长对于建立所需资源和技能以进一步有意义且有成效地扩大临床前PK/PD建模的使用是必要的。
