Gut instincts: CYP3A4 and intestinal drug metabolism.

The Journal of Clinical Investigation
Kenneth E Thummel


First-pass metabolism is a common cause of incomplete and variable absolute bioavailability for an orally dosed drug. The drug-metabolizing enzyme CYP3A4 is often implicated in this process, resulting, in some cases, in systemic exposures of less than 15% of the administered dose. By creating an elegant CYP3A4-transgenic mouse model, van Herwaarden et al. show in this issue of the JCI that first-pass metabolism of the anticancer agent docetaxel by the gut wall, and not the liver, is likely to be the major cause of its low oral bioavailability in humans (see the related article beginning on page 3583). This study helps explain interpatient differences in efficacy and safety following oral therapy with approved CYP3A4 substrates and provides a powerful new tool for preclinical predictions of first-pass metabolism for new drugs in development.


Nov 1, 1992·The Journal of Clinical Investigation·J C KolarsP B Watkins
Dec 14, 1991·Lancet·J C KolarsP B Watkins
Apr 1, 1990·Clinical Pharmacokinetics·D J Morgan
Oct 1, 1987·The Journal of Clinical Investigation·P B WatkinsP S Guzelian
Jul 1, 1996·Clinical Pharmacology and Therapeutics·M F PaineK E Thummel
May 23, 1998·Annual Review of Pharmacology and Toxicology·K E Thummel, G R Wilkinson
May 20, 1999·Annual Review of Pharmacology and Toxicology·F P Guengerich
Jun 6, 2000·Advanced Drug Delivery Reviews·D D ShenK E Thummel
May 23, 2002·Science·Makoto MakishimaDavid J Mangelsdorf
Nov 18, 2005·The Journal of Pharmacology and Experimental Therapeutics·Connie CheungFrank J Gonzalez
Nov 3, 2007·The Journal of Clinical Investigation·Antonius E van HerwaardenAlfred H Schinkel

❮ Previous
Next ❯


Apr 6, 2012·Archives of Pharmacal Research·Yu Kyung LeeYoung Hee Choi
Dec 12, 2012·Annals of Surgery·Sweta TandraRaj Vuppalanchi
Jul 27, 2012·Therapeutic Delivery·Patricia CallejaJuan M Irache
Apr 6, 2011·Expert Opinion on Drug Delivery·Maite AgüerosJuan M Irache
Feb 13, 2016·Journal of Pharmaceutical Sciences·Jenni KüblbeckPaavo Honkakoski
Oct 30, 2012·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Åsa SjöbergAnna-Lena Ungell
Sep 5, 2015·European Eating Disorders Review : the Journal of the Eating Disorders Association·James L Roerig, Kristine Steffen
Nov 21, 2015·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Kelli J GlennDietrich Tuerck
Aug 24, 2013·Drug Metabolism and Pharmacokinetics·Hankil SonKyungsoo Park
Feb 2, 2010·Trends in Pharmacological Sciences·Tamara J NicolsonRuth R A Roberts
May 12, 2018·Lipids in Health and Disease·Jyothshna Devi KatamreddyJaya Preethi Peesa
Nov 8, 2013·American Journal of Physiology. Cell Physiology·Kalpit ShahNeil A Bradbury
Sep 16, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Robert A B van WaterschootAlfred H Schinkel
Sep 26, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Li DiR Scott Obach
Feb 23, 2019·Journal of Pediatric Gastroenterology and Nutrition·Marie-Pier ThibaultJean-François Beaulieu
Sep 17, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Robert A B van WaterschootAlfred H Schinkel
May 1, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Haeyoung ZhangBhagwat Prasad
Apr 25, 2017·Environmental and Molecular Mutagenesis·Michael FasulloXinxin Ding
Aug 28, 2020·Frontiers in Bioengineering and Biotechnology·Steven N SteinwayDeok-Ho Kim
May 11, 2019·Journal of Experimental & Clinical Cancer Research : CR·Maria Karmella ApayaLie-Fen Shyur
Apr 26, 2019·Journal of Pediatric Gastroenterology and Nutrition·Marie-Pier ThibaultJean-François Beaulieu
Feb 4, 2021·Drug Development Research·Daniela FanniMirko Manchia
Mar 9, 2021·Frontiers in Pharmacology·Mohammed S AlqahtaniMuhammad Z Ahmad
May 7, 2021·Advanced Drug Delivery Reviews·Shahriar SharifiMorteza Mahmoudi
Dec 15, 2020·Pharmacology & Therapeutics·Alexis J BickJanet P Hapgood
Jan 10, 2009·Molecular Pharmaceutics·Mei-Ling Chen, Lawrence Yu
May 26, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Arianna FediSilvia Scaglione
Aug 9, 2019·Molecular Pharmaceutics·Aze WilsonRichard B Kim
Sep 4, 2021·Pharmacology & Therapeutics·Christopher M ArianKenneth E Thummel

❮ Previous
Next ❯

Methods Mentioned

gene knockout

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.

Related Papers

European Journal of Clinical Pharmacology
C G RegårdhC Shansky
The Journal of Pharmacology and Experimental Therapeutics
Aleksandra Galetin, J Brian Houston
European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Martin KuentzDieter Röthlisberger
© 2021 Meta ULC. All rights reserved