Advancing Predictions of Tissue and Intracellular Drug Concentrations Using In Vitro, Imaging and Physiologically Based Pharmacokinetic Modeling Approaches

Clinical Pharmacology and Therapeutics - Tập 104 Số 5 - Trang 865-889 - 2018
Yingying Guo1, Xiaoyan Chu2, Neil Parrott3, Kim L. R. Brouwer4, Vicky Hsu5, Swati Nagar6, Pär Matsson7, Pradeep Sharma8, Jan Snoeys9, Yuichi Sugiyama10, Daniel Tatosian2, Jashvant D. Unadkat11, Shiew‐Mei Huang5, Aleksandra Galetin12
1Investigational Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana,, USA
2Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co, Inc, Kenilworth, New Jersey, USA
3Pharmaceutical Sciences, Pharmaceutical Research and Early Development, Roche Innovation Centre Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland
4Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina,, USA
5Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA
6Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania,, USA
7Department of Pharmacy, Uppsala University, Uppsala, Sweden
8Safety and ADME Translational Sciences, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca R&D, Cambridge, UK
9Department of Pharmacokinetics, Dynamics, and Metabolism Janssen R&D Beerse Belgium
10Sugiyama Laboratory, RIKEN Innovation Center, RIKEN Research Cluster for Innovation, Yokohama, Japan
11Department of Pharmaceutics, University of Washington, Seattle, Washington, USA
12Centre for Applied Pharmacokinetic Research, School of Health Sciences, The University of Manchester, Manchester, UK.

Tóm tắt

This white paper examines recent progress, applications, and challenges in predicting unbound and total tissue and intra/subcellular drug concentrations using in vitro and preclinical models, imaging techniques, and physiologically based pharmacokinetic (PBPK) modeling. Published examples, regulatory submissions, and case studies illustrate the application of different types of data in drug development to support modeling and decision making for compounds with transporter‐mediated disposition, and likely disconnects between tissue and systemic drug exposure. The goals of this article are to illustrate current best practices and outline practical strategies for selecting appropriate in vitro and in vivo experimental methods to estimate or predict tissue and plasma concentrations, and to use these data in the application of PBPK modeling for human pharmacokinetic (PK), efficacy, and safety assessment in drug development.

Từ khóa


Tài liệu tham khảo

10.1016/j.xphs.2017.03.036

10.1038/clpt.2013.78

10.1007/s11095-014-1581-2

10.1002/cpt.437

10.1002/cpt.595

10.1016/j.clpt.2005.01.022

10.1007/s40262-015-0346-3

10.1074/jbc.M307938200

10.1146/annurev-pharmtox-011112-140309

10.1038/clpt.2013.45

10.1002/cpt.904

10.1021/mp4000822

10.1124/dmd.113.052134

10.1124/dmd.116.074575

10.1016/j.xphs.2017.03.025

10.1002/bdd.1823

10.1124/dmd.116.074823

10.1124/dmd.111.040477

10.1124/dmd.117.079152

10.1124/dmd.117.077115

10.1124/jpet.116.235689

10.1124/dmd.112.046193

10.1007/s11095-015-1753-8

10.1002/jps.20792

Francis L. Harrell A. Hallifax D.&Galetin A.Novel methodology for the isolation of lysosomes and measurement of intralysosomal drug accumulation.14th European ISSX Meeting Cologne Germany A5 (2017).

10.1007/s00249-008-0338-4

10.1021/acs.molpharmaceut.6b00908

10.1016/j.ejps.2017.08.014

10.1124/dmd.114.058032

10.1124/dmd.115.066647

10.1177/1087057115604141

10.1038/srep43047

10.1016/j.xphs.2017.04.056

10.1016/j.xphs.2017.04.054

10.1021/jm401963n

10.1124/dmd.116.074179

10.1124/dmd.111.040758

10.1021/acs.molpharmaceut.5b00453

10.1124/dmd.113.054783

10.1517/17425255.2013.741589

10.1016/j.xphs.2017.02.012

10.1124/dmd.114.062034

10.1124/dmd.116.071183

10.1124/dmd.118.080770

10.1021/acs.jproteome.5b00334

10.1208/s12248-017-0106-4

10.1021/acs.molpharmaceut.7b00364

10.1111/cts.12486

10.1124/dmd.114.059618

10.1124/dmd.116.074294

10.1016/j.ejps.2016.03.020

10.1124/dmd.116.071050

10.1002/cpt.409

10.1002/jcph.722

10.1124/jpet.113.206425

10.1038/psp.2012.21

10.1002/cpt.99

10.1002/nbm.2946

10.1148/radiol.12112061

10.1371/journal.pone.0095700

10.1007/s00330-016-4536-7

10.1038/psp.2014.24

10.1124/dmd.114.062174

10.1007/s40262-013-0117-y

10.1002/cpt.750

10.1124/jpet.116.237438

10.1002/cpt.807

10.1002/cpt.337

10.1002/cpt.206

10.1007/s40262-016-0476-2

10.1124/jpet.117.245712

10.2165/00003088-200645050-00006

10.1007/s11095-006-9210-3

10.1002/cpt.37

10.1038/clpt.2012.221

10.1007/s00228-016-2057-6

10.1093/jac/dkt423

10.1124/jpet.114.214536

10.1021/acs.biochem.6b00446

10.1038/s41598-018-22749-0

10.1124/dmd.116.069559

10.1124/dmd.116.073957

10.1002/cpt.176

10.1007/s40262-015-0328-5

10.1124/dmd.115.063362

10.1038/clpt.2014.55

10.1016/j.xphs.2017.04.057

10.1124/dmd.113.055558

10.1371/journal.pone.0080634

Takano A., 2006, Evaluation of in vivo P‐glycoprotein function at the blood‐brain barrier among MDR1 gene polymorphisms by using 11C‐verapamil, J. Nucl. Med., 47, 1427

10.1038/clpt.2010.11

10.1124/dmd.114.058685

10.2967/jnumed.113.130161

10.1002/cpt.362

10.1021/mp200160t

10.2967/jnumed.112.110254

10.2967/jnumed.111.098681

10.1016/j.xphs.2017.05.006

Shingaki T., 2015, Quantitative evaluation of mMate1 function based on minimally invasive measurement of tissue concentration using PET with [(11)C]metformin in mouse, Pharm. Res., 32, 2538

10.1002/cpt.701

10.1016/j.nucmedbio.2016.07.001

10.1016/j.nucmedbio.2013.03.006

10.1007/s40262-013-0097-y

10.1002/cpt.619

10.1124/dmd.114.058461

10.1007/s11095-014-1333-3

10.1016/j.ejps.2017.11.011

Ibrutinib clinical pharmacology review. <https://wwwaccessdatafdagov/drugsatfda_docs/nda/2013/205552Orig1s000ClinPharmRpdf> (2013).

Levonorgestrel clinical pharmacology review. <https://wwwaccessdatafdagov/drugsatfda_docs/nda/2013/203159Orig1s000ClinPharmRpdf>.

10.1111/cts.12421

Thông tin
Thông tin xuất bản

Clinical Pharmacology and Therapeutics

Tập 104 Số 5

865-889

Thông tin tác giả