Whole body physiologically-based pharmacokinetic models: their use in clinical drug development

Expert Opinion on Drug Metabolism & Toxicology
Andrea N EdgintonStefan Willmann

Abstract

Whole-body physiologically-based pharmacokinetic (WB-PBPK) models mathematically describe an organism as a closed circulatory system consisting of compartments that represent the organs important for compound absorption, distribution, metabolism and elimination. To review the current state of WB-PBPK model use in the clinical phases of drug development. A qualitative description of the WB-PBPK model structure is included along with a review of the varying methods available for input parameterisation. Current and potential WB-PBPK model application in clinical development is discussed. This modelling tool is at present used for small and large molecule drug development primarily as a means to scale pharmacokinetics from animals to humans based on physiology. The pharmaceutical industry is active in employing these models to clinical drug development although the applications in use now are narrow in comparison to the potential. Expanded integration of WB-PBPK models into the drug development process will only be achieved with staff training, managerial will, success stories and regulatory agency openness.

References

Apr 1, 1982·Journal of Pharmacokinetics and Biopharmaceutics·H Boxenbaum
Oct 1, 1994·Journal of Pharmacokinetics and Biopharmaceutics·R KawaiM Rowland
Sep 1, 1994·Environmental Health Perspectives·O AndersenL Scherrebeck
Jun 24, 1998·Risk Analysis : an Official Publication of the Society for Risk Analysis·E A BrownJ W Fisher
Nov 17, 1999·Journal of Pharmaceutical Sciences·I Mahmood
Feb 15, 2001·Journal of Pharmaceutical Sciences·P PoulinF P Theil
May 11, 2001·Journal of Toxicology and Environmental Health. Part a·J F YoungR H Luecke
Sep 29, 2001·Advanced Drug Delivery Reviews·B AgoramM B Bolger
Apr 8, 2003·Cancer Chemotherapy and Pharmacology·Jing Li, Peter R Gwilt
Apr 26, 2003·Journal of Toxicology and Environmental Health. Part a·Karine PriceKannan Krishnan
Sep 23, 2003·Journal of Pharmaceutical Sciences·Olivier LuttringerThierry Lavé
Nov 5, 2003·Critical Reviews in Toxicology·Paul S PriceDouglas R Tedder
Nov 19, 2003·Regulatory Toxicology and Pharmacology : RTP·C R KirmanM L Gargas
Apr 2, 2004·Toxicological Sciences : an Official Journal of the Society of Toxicology·Harvey J ClewellJustin G Teeguarden
Jun 15, 2004·Journal of Toxicology and Environmental Health. Part a·James V BrucknerJeffrey W Fisher
Jul 23, 2004·Journal of Medicinal Chemistry·Stefan WillmannJennifer B Dressman
Mar 1, 2005·Basic & Clinical Pharmacology & Toxicology·Massimiliano GermaniItalo Poggesi
Apr 26, 2005·BMC Anesthesiology·David G Levitt, Thomas W Schnider
Apr 29, 2005·Journal of Pharmaceutical Sciences·Trudy RodgersMalcolm Rowland
Nov 18, 2005·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·Kannan Krishnan, Gunnar Johanson
Dec 13, 2005·Annals of Biomedical Engineering·Gregory Z FerlJoseph J DiStefano
Dec 16, 2005·The AAPS Journal·Venkatesh A BhattaramJogarao V S Gobburu
Feb 14, 2006·Biochemical Pharmacology·Donald E Mager
Apr 28, 2006·Clinical Pharmacokinetics·Hannah M JonesThierry Lavé
Jul 5, 2006·Molecular Cancer Therapeutics·Gregory Z FerlJoseph J DiStefano
Aug 23, 2006·Expert Opinion on Drug Metabolism & Toxicology·Stefan WillmannWalter Schmitt
Sep 5, 2006·Risk Analysis : an Official Publication of the Society for Risk Analysis·Karen YokleyPaul M Schlosser
Sep 21, 2006·Clinical Pharmacokinetics·Andrea N EdgintonStefan Willmann
Dec 29, 2006·Chemistry & Biodiversity·Christian Lüpfert, Andreas Reichel
Feb 15, 2007·Journal of Applied Toxicology : JAT·Weihsueh A ChiuKannan Krishnan
Apr 13, 2007·Expert Opinion on Drug Metabolism & Toxicology·Ivan Nestorov
May 8, 2007·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Massimiliano GermaniItalo Poggesi
May 8, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Hugh A BartonYu-Mei Tan
May 16, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Wederson Marcos ClaudinoAngelo Di Leo

❮ Previous
Next ❯

Citations

Jul 27, 2011·Cancer Chemotherapy and Pharmacology·Gisela KerstingGeorg Hempel
Aug 26, 2011·Journal of Pharmacokinetics and Pharmacodynamics·Kyeong-Ryoon LeeSuk-Jae Chung
Dec 14, 2011·Journal of Pharmacokinetics and Pharmacodynamics·John F GrafMaria I Zavodszky
Jan 10, 2013·Clinical Pharmacokinetics·Miroslav DostalekManoranjenni Chetty
Oct 15, 2013·International Journal of Pharmaceutics·Henry T PengBob Cheung
Nov 26, 2009·Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment·Ian C MunroShahrzad Tafazoli
Dec 28, 2012·The AAPS Journal·Hannah M JonesPatrick Poulin
Dec 14, 2011·Drug Metabolism and Drug Interactions·Xavier Boulenc, Olivier Barberan
Apr 23, 2013·Toxicology and Applied Pharmacology·Jessica J VamathevanPhilippe Sanseau
May 3, 2011·Archives of Toxicology·Sarah AdlerJosé-Manuel Zaldivar
Sep 22, 2010·Annual Review of Pharmacology and Toxicology·Malcolm RowlandGeoffrey Tucker
Oct 23, 2009·Pharmaceutical Research·Peter ThygesenAchiel Van Peer
Mar 17, 2010·Expert Review of Clinical Pharmacology·Steven E Kern
Mar 1, 2009·Expert Review of Clinical Pharmacology·Nikoletta Fotaki
Mar 6, 2015·Expert Opinion on Drug Metabolism & Toxicology·Iftekhar Mahmood
Jul 19, 2011·Expert Opinion on Drug Metabolism & Toxicology·Andrea N Edginton, Ghanashyam Joshi
Sep 24, 2011·Expert Opinion on Drug Metabolism & Toxicology·Jennifer B DressmanStefan Willmann
Mar 1, 2009·Expert Opinion on Drug Discovery·Scott Summerfield, Phil Jeffrey
Jul 16, 2009·Drug Metabolism Reviews·Pascal EspiéJean-Baptiste Watelet
Jun 2, 2009·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·C R GibsonE Mulrooney
Jan 5, 2010·Toxicology and Applied Pharmacology·Lei ZhangShiew-Mei Huang
Sep 4, 2015·Quarterly Reviews of Biophysics·Yulan WangHualiang Jiang
Aug 2, 2015·Journal of Pharmacokinetics and Pharmacodynamics·Thierry WendlingLeon Aarons
Jun 11, 2009·British Journal of Pharmacology·Vijay Sharma, John H McNeill
Jun 13, 2012·The Journal of Pharmacy and Pharmacology·Stefan WillmannJörg Lippert
Feb 16, 2011·Paediatric Anaesthesia·Brian J Anderson, Nick H G Holford
Feb 9, 2012·The Journal of Pharmacy and Pharmacology·Helen GrahamLeon Aarons
Nov 3, 2010·Paediatric Anaesthesia·Alison H Thomson, Henry L Elliott
Apr 10, 2015·British Journal of Clinical Pharmacology·Hannah Katharine Batchelor, John Francis Marriott
Nov 26, 2009·Journal of Magnetic Resonance Imaging : JMRI·Jean-Marc IdéeClaire Corot
Oct 30, 2014·CPT: Pharmacometrics & Systems Pharmacology·A R Maharaj, A N Edginton
Sep 20, 2015·Clinical Pharmacokinetics·Ruben de KanterAlexander Treiber

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.