PMID: 24695277Apr 4, 2014Paper

Evaluation of human hepatocytes cultured by three-dimensional spheroid systems for drug metabolism

Drug Metabolism and Pharmacokinetics
Takako OhkuraTakuo Ogihara


We investigated the utility of three-dimensional (3D) spheroid cultures of human hepatocytes in discovering drug metabolites. Metabolites of acetaminophen, diclofenac, lamotrigine, midazolam, propranolol and salbutamol were analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS) to measure enzyme activities in this system cultured for 2 and 7 days. Sequential metabolic reactions by Phase I and then Phase II enzymes were found in diclofenac [CYP2C9 and UDP-glucuronyltransferases (UGTs)], midazolam (CYP3A4 and UGTs) and propranolol (CYP1A2/2D6 and UGTs). Moreover, lamotrigine and salbutamol were metabolized to lamotrigine-N-glucuronide and salbutamol 4-O-sulfate, respectively. These metabolites, which are human specific, could be observed in clinical studies, but not in conventional hepatic culture systems as in previous reports. Acetaminophen was metabolized to glucuronide and sulfate conjugates, and N-acetyl-p-benzo-quinoneimine (NAPQI) and its metabolites were not observed. In addition, mRNA of drug-metabolism enzymes [CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, UGT1A1, UGT2B7, sulfotransferase 1A1 (SULT1A1) and glutathione S-transferase pi 1 (GSTP1)], which were measured by qRT-PCR, were expressed in the hu...Continue Reading


Dec 1, 1988·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·P H DegenU Sinterhauf
Nov 1, 1986·British Journal of Clinical Pharmacology·D J MorganS P Ziccone
Oct 1, 1980·British Journal of Clinical Pharmacology·L F Prescott
Jan 1, 1982·Developmental Pharmacology and Therapeutics·C Gardey-LevassortG Olive
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jul 23, 2003·Current Drug Metabolism·Wei Tang
Mar 28, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Andrew RowlandJohn O Miners
Jun 17, 2006·Biochemical and Biophysical Research Communications·Masuhiro NishimuraShinsaku Naito
Apr 6, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Wei Lu, Jack P Uetrecht
May 19, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Micaela C DamstenNico P E Vermeulen
Jan 31, 2008·Birth Defects Research. Part A, Clinical and Molecular Teratology·Araba A AdjeiJ Steven Leeder
Feb 8, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sylvie KlieberGérard Fabre
Sep 19, 2008·Expert Opinion on Drug Metabolism & Toxicology·André Guillouzo, Christiane Guguen-Guillouzo
Jan 14, 2009·Chemical Research in Toxicology·Shelby AndersonMary Pat Knadler
Mar 11, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Patricio GodoySteven Dooley
Apr 18, 2009·British Journal of Clinical Pharmacology·Ruth HylandBarry Jones
Aug 15, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Zoe RichesMichael W H Coughtrie
Sep 25, 2009·Cell Transplantation·Yoshitaka MiyamotoShin Enosawa
Jul 3, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Wendy WeiWei WangR Scott Obach
Feb 1, 1997·Toxicology in Vitro : an International Journal Published in Association with BIBRA·P Ammann, P Maier

❮ Previous
Next ❯


Dec 23, 2015·Journal of Applied Toxicology : JAT·M José Gómez-LechónM Teresa Donato
Apr 20, 2016·International Journal of Molecular Sciences·Fanny KnöspelKatrin Zeilinger
Jan 27, 2015·Journal of Laboratory Automation·Salman R KhetaniBrenton R Ware
Jul 8, 2016·Experimental Biology and Medicine·Katrin ZeilingerFanny Knöspel
Nov 17, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Kenneth C Cassidy, Ping Yi
Oct 14, 2017·Journal of Applied Toxicology : JAT·Bokyeong RyuJae-Hak Park
May 17, 2019·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Takuo OgiharaHajime Kojima
Jul 19, 2017·The Journal of Toxicological Sciences·Takuo OgiharaHajime Kojima
Nov 19, 2019·Toxicology Mechanisms and Methods·Izumi IdeNatsumi Mizoguchi
Jan 14, 2020·Bioscience, Biotechnology, and Biochemistry·Yusaku Inubushi, Akira Tachibana
Oct 1, 2019·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Silvi A ChackoJinping Gan
Jan 1, 2015·Microarrays·Anastasia BachmannAndreas K Nussler
Dec 6, 2016·Frontiers in Pharmacology·Benjamin BergerManuel Haschke
May 13, 2020·In Vitro Cellular & Developmental Biology. Animal·Takayuki HiranoTakeshige Otoi
Aug 23, 2019·FEBS Letters·Takeshi KatsudaTakahiro Ochiya
Apr 3, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Yitong LiuRobert L Sprando
Oct 17, 2020·Seizure : the Journal of the British Epilepsy Association·Janthima Methaneethorn, Nattawut Leelakanok

❮ Previous
Next ❯

Related Concepts

Trending Feeds


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 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.


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.