The disposition and metabolism of zibotentan (ZD4054): an oral-specific endothelin A receptor antagonist in mice, rats and dogs

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Jacqueline A Clarkson-JonesHelen Tomkinson


Zibotentan (ZD4054) is an oral-specific endothelin A receptor antagonist in development for the treatment of castration-resistant prostate cancer. In a number of preclinical studies, the disposition and metabolism of zibotentan were investigated in mice, rats and dogs. Following oral and intravenous administration, zibotentan was slowly absorbed (maximal concentration at approximately 4 h) and rapidly excreted, with the majority being eliminated by 48 h. The main route of elimination was via the urine in dogs and female rats, but via the faeces in male rats and mice of both sexes. Zibotentan was moderately bound to plasma proteins of all species examined (55-95%), and widely distributed throughout all tissues with the highest concentrations seen in the organs of excretion. Zibotentan was moderately metabolised. Zibotentan was well absorbed, moderately bound to plasma proteins, widely distributed and excreted predominantly via the urine.


Jul 1, 1997·Toxicology and Industrial Health·R P BrownR P Beliles
Jun 20, 1998·The Journal of Biological Chemistry·M OkazawaT Masaki
Aug 26, 1998·Drug Metabolism Reviews·C A Mugford, G L Kedderis
Jun 18, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·James M BradyCurtis D Klaassen
Jul 9, 2002·Investigational New Drugs·E Scott KopetzMichael Carducci
Feb 4, 2003·Nature Reviews. Cancer·Joel B NelsonPerry Nisen
May 1, 1955·The American Journal of Physiology·L A SAPIRSTEING HANUSEK
Oct 3, 2003·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Yukiyoshi FujitaTatsuji Iga
May 29, 2004·Journal of Translational Medicine·A Bagnato, Pier Giorgio Natali
Jun 15, 2004·Public Health Reports·Kathleen McDavidTrevor D Thompson
Oct 8, 2004·The New England Journal of Medicine·Daniel PetrylakE David Crawford
Mar 18, 2006·Molecular Endocrinology·David J Waxman, Caitlin O'Connor
Apr 25, 2006·The Urologic Clinics of North America·Susan Kasper, Michael S Cookson
Aug 13, 2008·Biopharmaceutics & Drug Disposition·Si H YangMyung G Lee
Jul 9, 2010·CA: a Cancer Journal for Clinicians·Ahmedin JemalElizabeth Ward

Related Concepts

Metabolic Biotransformation
Serum Proteins
High Pressure Liquid Chromatography Procedure
Canis familiaris
Plasma Protein Binding Capacity
Drug or Chemical Tissue Distribution
Receptor, Endothelin A

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