Comparison of Fraction Unbound Between Liver Homogenate and Hepatocytes at 4°C.

The AAPS Journal
Keith RiccardiLi Di

Abstract

Fraction unbound (fu) values obtained from liver or hepatocyte homogenate with equilibrium dialysis (fu,homo) or the hepatocyte partition coefficient method at 4°C (fu,c) are both frequently used to estimate unbound drug concentrations (Cu) and unbound partition coefficient (Kpuu) of the liver. Literature data are somewhat controversial on this topic: some reported that the two methods gave comparable fu values, while others showed that they had no correlation. To better understand the two approaches, 44 structurally diverse compounds with wide ranges of fu values were used for the comparison study. The results indicate that fu values from the two methods are comparable with an average fold error of 2.9-fold and a bias of 1.0. Although some outliers were observed, the reasons are not entirely clear and further investigations are needed. As the fu data from both methods are correlated, fu,homo measurement using tissue homogenate is recommended over cells at 4°C (fu,c) in early drug discovery. This is because fu,homo method is more reliable, has good in vivo predictability, and feasibility for any tissue types where representative cells may not be readily available. The approach can be used to estimate Cu and Kpuu of tissues in o...Continue Reading

References

Nov 17, 2004·Advances in Physiology Education·Walter F Boron
Jul 7, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yoshiyuki YabeJ Brian Houston
Dec 14, 2011·Journal of Pharmaceutical Sciences·Li DiTristan S Maurer
Mar 5, 2014·Frontiers in Physiology·Vernon A RuffinMark D Parker
Mar 8, 2014·Journal of Medicinal Chemistry·André MateusPer Artursson
Sep 6, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Bridget L MorseYurong Lai
Jul 16, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Keith RiccardiLi Di
Mar 5, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Keith RiccardiLi Di
Apr 8, 2017·Journal of Pharmaceutical Sciences·Julia RiedeBirk Poller
May 5, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Takashi YoshikadoYuichi Sugiyama
Feb 14, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Keith RiccardiLi Di
Mar 21, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ken-Ichi KanekoYasuyoshi Watanabe
Oct 27, 2018·Biopharmaceutics & Drug Disposition·Sangwoo RyuLi Di
Feb 23, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Keith A RiccardiRui Li
Nov 17, 2019·European Journal of Medicinal Chemistry·Christine C OrozcoLi Di

❮ Previous
Next ❯

Citations

Sep 17, 2021·Planta medica·Deborah SpiessAna Paula Simões-Wüst

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsy
equilibrium dialysis

Software Mentioned

Analyst
MoKa
MultiQuant

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.