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Physiologically-Based Pharmacokinetic Models for Evaluating Membrane Transporter Mediated Drug-Drug Interactions: Current Capabilities, Case Studies, Future Opportunities, and Recommendations.
Clinical Pharmacology & Therapeutics ( IF 6.7 ) Pub Date : 2019-12-31 , DOI: 10.1002/cpt.1693
Kunal S Taskar 1 , Venkatesh Pilla Reddy 2 , Howard Burt 3 , Maria M Posada 4 , Manthena Varma 5 , Ming Zheng 6 , Mohammed Ullah 7 , Arian Emami Riedmaier 8 , Ken-Ichi Umehara 7 , Jan Snoeys 9 , Masanori Nakakariya 10 , Xiaoyan Chu 11 , Maud Beneton 12 , Yuan Chen 13 , Felix Huth 14 , Rangaraj Narayanan 15 , Dwaipayan Mukherjee 8 , Vaishali Dixit 16 , Yuichi Sugiyama 17 , Sibylle Neuhoff 3
Affiliation  

Physiologically-based pharmacokinetic (PBPK) modeling has been extensively used to quantitatively translate in vitro data and evaluate temporal effects from drug-drug interactions (DDIs), arising due to reversible enzyme and transporter inhibition, irreversible time-dependent inhibition, enzyme induction, and/or suppression. PBPK modeling has now gained reasonable acceptance with the regulatory authorities for the cytochrome-P450-mediated DDIs and is routinely used. However, the application of PBPK for transporter-mediated DDIs (tDDI) in drug development is relatively uncommon. Because the predictive performance of PBPK models for tDDI is not well established, here, we represent and discuss examples of PBPK analyses included in regulatory submission (the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Pharmaceuticals and Medical Devices Agency (PMDA)) across various tDDIs. The goal of this collaborative effort (involving scientists representing 17 pharmaceutical companies in the Consortium and from academia) is to reflect on the use of current databases and models to address tDDIs. This challenges the common perceptions on applications of PBPK for tDDIs and further delves into the requirements to improve such PBPK predictions. This review provides a reflection on the current trends in PBPK modeling for tDDIs and provides a framework to promote continuous use, verification, and improvement in industrialization of the transporter PBPK modeling.

中文翻译:

用于评估膜转运蛋白介导的药物-药物相互作用的基于生理的药代动力学模型:当前能力,案例研究,未来机会和建议。

基于生理学的药代动力学(PBPK)建模已广泛用于定量翻译体外数据并评估由于可逆的酶和转运蛋白抑制,不可逆的时间依赖性抑制,酶诱导以及药物诱导的药物-药物相互作用(DDI)产生的时间效应。 /或抑制。PBPK模型现在已经获得了监管机构对细胞色素P450介导的DDI的合理认可,并已被常规使用。但是,PBPK在药物开发中运用于转运蛋白介导的DDI(tDDI)方面并不常见。由于尚未完全建立PBPK模型对tDDI的预测性能,因此,在这里,我们代表并讨论了监管文件(美国食品药品管理局(FDA),欧洲药品管理局(EMA),以及跨各种tDDI的药品和医疗器械局(PMDA)。这项合作努力的目的(让代表17个制药公司的联合制药公司和来自学术界的科学家参与进来)的目的是反思使用当前数据库和模型来解决tDDI的问题。这挑战了将PBPK用于tDDI的普遍认识,并进一步研究了改进此类PBPK预测的要求。这篇综述反映了针对tDDI的PBPK建模的当前趋势,并提供了一个框架,以促进转运蛋白PBPK建模的连续使用,验证和工业化改进。这项合作努力的目的(让代表17个制药公司的联合制药公司和来自学术界的科学家参与进来)的目的是反思使用当前数据库和模型来解决tDDI的问题。这挑战了将PBPK用于tDDI的普遍认识,并进一步研究了改进此类PBPK预测的要求。这篇综述反映了针对tDDI的PBPK建模的当前趋势,并提供了一个框架,以促进转运蛋白PBPK建模的连续使用,验证和工业化改进。这项合作努力的目的(让代表17个制药公司的联合制药公司和来自学术界的科学家参与进来)的目的是反思使用当前数据库和模型来解决tDDI的问题。这挑战了将PBPK用于tDDI的普遍认识,并进一步研究了改进此类PBPK预测的要求。这篇综述反映了针对tDDI的PBPK建模的当前趋势,并提供了一个框架,以促进转运蛋白PBPK建模的连续使用,验证和工业化改进。
更新日期:2019-12-31
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