Application of New Cellular and Microphysiological Systems to Drug Metabolism Optimization and Their Positioning Respective to In Silico Tools

SLAS Discovery
Luca DocciStephen Fowler

Abstract

New cellular model systems for drug metabolism applications, such as advanced 2D liver co-cultures, spheroids, and microphysiological systems (MPSs), offer exciting opportunities to reproduce human biology more closely in vitro with the aim of improving predictions of pharmacokinetics, drug-drug interactions, and efficacy. These advanced cellular systems have quickly become established for human intrinsic clearance determination and have been validated for several other absorption, distribution, metabolism, and excretion (ADME) applications. Adoption will be driven through the demonstration of clear added value, for instance, by more accurate and precise clearance predictions and by more reliable extrapolation of drug interaction potential leading to faster progression to pivotal proof-of-concept studies. New experimental systems are attractive when they can (1) increase experimental capacity, removing optimization bottlenecks; (2) improve measurement quality of ADME properties that impact pharmacokinetics; and (3) enable measurements to be made that were not previously possible, reducing risk in ADME prediction and candidate selection. As new systems become established, they will find their place in the repository of tools use...Continue Reading

References

Feb 1, 1994·Clinical Pharmacokinetics·D R Krishna, U Klotz
Mar 27, 2001·Drug Discovery Today·A P. Li
Oct 2, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ramiro JoverJosé V Castell
Nov 16, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yau Yi LauK-C Cheng
Aug 3, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Dermot F McGinnityRobert J Riley
Jul 29, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Anthony AtkinsonKen Grime
Nov 22, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Brian W OgilvieAndrew Parkinson
Feb 3, 2007·Chemico-biological Interactions·Albert P Li
Oct 31, 2007·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·N J HewittS S Ferguson
Nov 21, 2007·Nature Biotechnology·Salman R Khetani, Sangeeta N Bhatia
Nov 21, 2009·Biochemical Pharmacology·Eric NovikMartin L Yarmush
Jan 16, 2010·Expert Opinion on Drug Metabolism & Toxicology·Piyun ChaoK C Cheng
Mar 2, 2010·Nature Reviews. Drug Discovery·UNKNOWN International Transporter ConsortiumLei Zhang
Jun 1, 1994·Toxicology in Vitro : an International Journal Published in Association with BIBRA·P Skett
Sep 17, 2010·Current Drug Discovery Technologies·Jasminder SahiCornelia Smith
Oct 20, 2010·Expert Opinion on Drug Metabolism & Toxicology·Odette A Fahmi, Sharon L Ripp
Aug 13, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yuan ChenAdrian J Fretland
Aug 21, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tom S ChanDonald Tweedie
Dec 25, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Diane RamsdenYongmei Li
Apr 4, 2014·Drug Metabolism and Pharmacokinetics·Takako OhkuraTakuo Ogihara
Jul 1, 2014·Nature Communications·Olivier FreyAndreas Hierlemann
Sep 25, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Nenad ManevskiKarine Litherland
Dec 3, 2014·Expert Opinion on Drug Metabolism & Toxicology·Vinícius Gonçalves MaltarolloKathia Maria Honorio
Jan 9, 2015·The AAPS Journal·Li Di, R Scott Obach
Feb 11, 2015·Expert Opinion on Drug Metabolism & Toxicology·Robert J Riley, Claire E Wilson
May 1, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ujjal SarkarSteven R Tannenbaum
Jun 17, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Diane RamsdenDonald J Tweedie
Sep 13, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·J Matthew HutzlerShelby R Anderson
Oct 11, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Christine LinSalman R Khetani
Nov 27, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Thomas Eric BallardR Scott Obach
Nov 28, 2015·Expert Opinion on Drug Metabolism & Toxicology·Zdenek Dvorak
Dec 15, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Vaishali DixitNiresh Hariparsad
Mar 17, 2016·Archives of Toxicology·Hassan RashidiDavid C Hay

❮ Previous
Next ❯

Software Mentioned

Silico
HepatoPac
ADME
GraphPad Prism
In

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.