DMPK, Research and Early Development, Oncology R&D, AstraZeneca, Boston, Massachusetts, USA.
Takeda Development Center Americas, Inc., Cambridge, Massachusetts, USA.
Clin Pharmacol Ther. 2022 Oct;112(4):770-781. doi: 10.1002/cpt.2503. Epub 2021 Dec 24.
The International Consortium for Innovation and Quality (IQ) Physiologically Based Pharmacokinetic (PBPK) Modeling Induction Working Group (IWG) conducted a survey across participating companies around general strategies for PBPK modeling of induction, including experience with its utility to address various questions, regulatory interactions, and regulatory acceptance. The results highlight areas where PBPK modeling is used with high confidence and identifies opportunities where confidence is lower and further evaluation is needed. To enhance the survey results, the PBPK-IWG also collected case studies and analyzed recent literature examples where PBPK models were applied to predict CYP3A induction-mediated drug-drug interactions. PBPK modeling of induction has evolved and progressed significantly, proving to have great potential to accelerate drug discovery and development. With the aim of enabling optimal use for new molecular entities that are either substrates and/or inducers of CYP3A, the PBPK-IWG proposes initial workflows for PBPK application, discusses future trends, and identifies gaps that need to be addressed.
国际创新与质量联盟（IQ）生理基于药代动力学（PBPK）建模诱导工作组（IWG）对参与公司进行了一项调查，内容涉及 PBPK 诱导建模的一般策略，包括其在解决各种问题、监管互动和监管接受方面的应用经验。调查结果突出了 PBPK 建模具有高度置信度的领域，并确定了信心较低且需要进一步评估的领域。为了增强调查结果，PBPK-IWG 还收集了案例研究，并分析了最近应用 PBPK 模型预测 CYP3A 诱导介导的药物相互作用的文献实例。诱导的 PBPK 建模已经有了显著的发展和进步，证明其在加速药物发现和开发方面具有巨大的潜力。为了使 CYP3A 的底物和/或诱导剂的新分子实体能够得到最佳利用，PBPK-IWG 提出了 PBPK 应用的初始工作流程，讨论了未来的趋势，并确定了需要解决的差距。
