Investigation of the inhibitory effects of various drugs on the hepatic uptake of fexofenadine in humans

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Soichiro MatsushimaYuichi Sugiyama

Abstract

Fexofenadine (FEX), an H(1)-receptor antagonist, is eliminated from the liver mainly in an unchanged form. Our previous study suggested that organic anion-transporting polypeptide (OATP) 1B3 contributes mainly to the hepatic uptake of FEX. On the other hand, a clinical report demonstrated that a T521C mutation of OATP1B1 increased its plasma area under the plasma concentration-time curve. Several compounds are reported to have a drug interaction with FEX, and some of this may be caused by the inhibition of its hepatic uptake. We determined which transporters are involved in the hepatobiliary transport of FEX by using double transfectants and examined whether clinically reported drug interactions with FEX could be explained by the inhibition of its hepatic uptake. Vectorial basal-to-apical transport of FEX was observed in double transfectants expressing OATP1B1/multidrug resistance-associated protein 2 (MRP2) and OATP1B3/MRP2, suggesting that OATP1B1 as well as OATP1B3 is involved in the hepatic uptake of FEX and that MRP2 can recognize FEX as a substrate. The inhibitory effects of compounds on FEX uptake in OATP1B3-expressing HEK293 cells were investigated, and the maximal degree of increase in plasma AUC of FEX by drug interac...Continue Reading

References

Nov 1, 1982·Journal of Pharmaceutical Sciences·A SelenP G Welling
Nov 1, 1981·Journal of Pharmacobio-dynamics·K YamaokaT Uno
Mar 10, 2001·Clinical Pharmacology and Therapeutics·M A HammanS D Hall
Jan 23, 2003·The Journal of Pharmacology and Experimental Therapeutics·Yoshihisa ShitaraYuichi Sugiyama
Oct 31, 2003·Clinical Pharmacology and Therapeutics·Christer TannergrenHans Lennernäs
May 26, 2004·The Journal of Pharmacology and Experimental Therapeutics·Masaru HiranoYuichi Sugiyama
Oct 28, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Mizuki NinomiyaToshiharu Horie
Jan 8, 2005·Clinical Pharmacology and Therapeutics·Norio Yasui-FurukoriTomonori Tateishi
Apr 12, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Harunobu TaharaYuichi Sugiyama
Apr 12, 2005·Annual Review of Pharmacology and Toxicology·Yoshihisa ShitaraYuichi Sugiyama
Apr 22, 2005·British Journal of Clinical Pharmacology·Mikko NiemiMartin F Fromm
Jun 16, 2005·Molecular Pharmacology·Masaru HiranoYuichi Sugiyama
Jul 15, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Maki ShimizuYuichi Sugiyama
Feb 4, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Harunobu TaharaYuichi Sugiyama
Apr 6, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Masaru HiranoYuichi Sugiyama
May 4, 2006·British Journal of Clinical Pharmacology·Mikiko ShimizuTomonori Tateishi
Jun 27, 2006·British Journal of Clinical Pharmacology·Mikiko ShimizuTomonori Tateishi
Jul 1, 2006·Journal of Clinical Pharmacology·Rolf P G van HeeswijkD William Cameron
Aug 15, 2006·The Journal of Pharmacology and Experimental Therapeutics·Justine L LamLeslie Z Benet
Aug 25, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tsukasa UnoTomonori Tateishi
Aug 29, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Mizuki NinomiyaToshiharu Horie

❮ Previous
Next ❯

Citations

Mar 2, 2010·Nature Reviews. Drug Discovery·UNKNOWN International Transporter ConsortiumLei Zhang
Jul 31, 2010·Nature Reviews. Drug Discovery·Kiyohiko SuganoFrank Senner
Aug 22, 2009·Journal of the American Society of Nephrology : JASN·Thomas D NolinJonathan Himmelfarb
Dec 22, 2011·Drug Metabolism and Pharmacokinetics·Takeo Nakanishi, Ikumi Tamai
Oct 29, 2013·Annual Review of Pharmacology and Toxicology·Nathan D PfeiferKim L R Brouwer
May 7, 2009·Expert Opinion on Drug Metabolism & Toxicology·Jürgen KindlaJörg König
May 20, 2008·Expert Opinion on Drug Metabolism & Toxicology·Anne T NiesDietrich Keppler
Jul 16, 2009·Drug Metabolism Reviews·Margherita Strolin BenedettiJean-Baptiste Watelet
Jul 16, 2009·Drug Metabolism Reviews·Alan BoobisKeith Tipton
Sep 16, 2010·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yumiko AkamineTsukasa Uno
Mar 12, 2015·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yumiko Akamine
Oct 18, 2016·Journal of Ginseng Research·Dal-Sik KimMin-Gul Kim
Mar 20, 2013·Molecular Aspects of Medicine·Kazuya Maeda, Yuichi Sugiyama
Feb 25, 2011·Advanced Drug Delivery Reviews·Kazuya Maeda, Yuichi Sugiyama
Sep 30, 2009·British Journal of Pharmacology·A Kalliokoski, M Niemi
Mar 14, 2013·Basic & Clinical Pharmacology & Toxicology·Victoria C ZiesenitzGerd Mikus
Jun 8, 2011·Journal of Clinical Pharmacology·Christine Y MalatiScott R Penzak
Jul 24, 2014·CPT: Pharmacometrics & Systems Pharmacology·A YamadaY Sugiyama
Aug 27, 2014·Biopharmaceutics & Drug Disposition·Takeo Nakanishi, Ikumi Tamai
Nov 15, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Katherine S FennerHugh A Barton
May 15, 2015·Pharmaceutical Research·Robert GharaviHazem E Hassan
Aug 21, 2012·Biochemical Pharmacology·Annett KunzeHeike Gutmann
Oct 27, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yuri TsuruyaHiroyuki Kusuhara
Mar 11, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Imad HannaBing Zhu
Apr 11, 2018·Expert Opinion on Drug Metabolism & Toxicology·Yumiko Akamine, Masatomo Miura
Nov 24, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yuichi Uwai
Mar 11, 2010·Clinical Pharmacokinetics·Joseph D MaAnne N Nafziger
Feb 24, 2018·Current Medicinal Chemistry·Carolina I Ghanem, Jose E Manautou
Mar 29, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jae H ChangJonathan Cheong
Nov 22, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Evita van de SteegAlfred H Schinkel
Dec 17, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Soichiro MatsushimaYuichi Sugiyama
Jun 4, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yunpeng XiaoMei Hong
Nov 2, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hiroyuki KusuharaYuichi Sugiyama
Feb 5, 2008·Molecular Pharmacology·Soichiro MatsushimaYuichi Sugiyama

❮ 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.