Comparison of human cytochrome P450 inhibition by the thienopyridines prasugrel, clopidogrel, and ticlopidine

Drug Metabolism and Pharmacokinetics
K HagiharaT Ikeda

Abstract

Differences in the inhibition of cytochrome P450 activities among thienopyridine antiplatelet agents, ticlopidine, clopidogrel, prasugrel, and the metabolites, 2-oxo-clopidogrel, clopidogrel acid metabolite, deacetylated metabolite of prasugrel (R-95913) and the pharmacologically active metabolites of clopidogrel and prasugrel, were examined using recombinant cytochromes P450 and fluorescent probe substrates. Ticlopidine and clopidogrel inhibited CYP2B6 with IC(50) values of 0.0517+/-0.0323 microM and 0.0182+/-0.0069 microM, respectively, and inhibited CYP2C19 with IC(50) values of 0.203+/-0.124 microM and 0.524+/-0.160 microM, respectively. Ticlopidine also inhibited CYP2D6 (IC(50) of 0.354+/-0.158 microM). In contrast, 2-oxo-clopidogrel, prasugrel and R-95913 were much weaker inhibitors of CYP2B6, CYP2C19 and CYP2D6. The inhibitory effects of all the compounds tested were much weaker on the isoforms other than those indicated above. The active metabolites of clopidogrel and prasugrel and clopidogrel acid metabolite also did not affect the activities of the P450s examined.

References

Dec 9, 1997·Clinical Pharmacology and Therapeutics·S R DonahueJ W Ko
May 8, 1999·British Journal of Clinical Pharmacology·T TateishiS Kobayashi
Oct 18, 2003·The Journal of Pharmacology and Experimental Therapeutics·Tanja RichterUlrich M Zanger
Jan 8, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Deepak K Dalvie, Thomas N O'Connell
May 19, 2004·British Journal of Pharmacology·Kenji YonedaSei Kobayashi
May 25, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Miia TurpeinenOlavi Pelkonen
Oct 21, 2004·JAMA : the Journal of the American Medical Association·Steven P Schulman
Apr 27, 2005·Seminars in Thrombosis and Hemostasis·Pierre Savi, Jean-Marc Herbert
Jun 18, 2005·Clinical Pharmacology and Therapeutics·Miia TurpeinenKari Laine
Jan 18, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jessica L Fayer RehmelBarbara J Ring
Dec 13, 2006·Rapid Communications in Mass Spectrometry : RCM·Nagy A FaridHenrianna Pang
Apr 4, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Nagy A FaridMark J Goldberg
Dec 21, 2007·Journal of Clinical Pharmacology·Nagy A FaridDavid S Small
Mar 29, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Eric T WilliamsNagy A Farid

❮ Previous
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Citations

Jul 30, 2009·European Heart Journal·Céline VerstuyftRichard B Kim
Feb 22, 2013·European Heart Journal·Stefan AgewallUNKNOWN ESC Working Group on Cardiovascular Pharmacology and Drug Therapy and ESC Working Group on Thrombosis
Apr 20, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·James R Halpert
Mar 16, 2011·Drug Metabolism and Pharmacokinetics·Noriyuki Koyama, Yasushi Yamazoe
Mar 29, 2014·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Tommy AnderssonLars Wallentin
Jul 12, 2014·European Journal of Clinical Pharmacology·Jean-Philippe ColletUNKNOWN DOSAPI investigators
Jan 8, 2013·Expert Opinion on Drug Metabolism & Toxicology·Jawed FareedIndermohan Thethi
Jul 17, 2009·Expert Opinion on Investigational Drugs·Nicholas B Norgard
Oct 27, 2012·The Annals of Thoracic Surgery·Victor A FerrarisUNKNOWN Society of Thoracic Surgeons
Jan 2, 2016·Pharmacological Reviews·Janne T BackmanPertti J Neuvonen
Sep 8, 2011·Fundamental & Clinical Pharmacology·Karsten SchrörKurt Huber
Mar 21, 2012·British Journal of Pharmacology·V AncrenazY Daali
Feb 13, 2013·Environmental and Molecular Mutagenesis·Michael M Iba, Robert J Caccavale
Jan 7, 2011·Journal of Clinical Pharmacology·Jung-Woo BaeSeok-Young Lee
Aug 26, 2010·British Journal of Pharmacology·Anja ZahnoStephan Krähenbühl
Sep 27, 2014·Biopharmaceutics & Drug Disposition·Xinmeng ChenMin Huang
Jul 15, 2009·Annales pharmaceutiques françaises·M-M Samama, I Elalamy
Oct 23, 2010·Pharmacology & Therapeutics·Hong-Guang XieShao-Liang Chen
Jul 13, 2012·Expert Opinion on Pharmacotherapy·Young-Hoon JeongPaul A Gurbel
Jul 9, 2010·Drug Metabolism and Pharmacokinetics·Noritaka AriyoshiMitsukazu Kitada
Mar 25, 2014·Clinical Biochemistry·Radu M NanauManuela G Neuman
Jul 10, 2016·Fundamental & Clinical Pharmacology·Alphienes Stanley XavierDeepak Gopal Shewade
May 28, 2009·The Annals of Pharmacotherapy·Nicholas B NorgardGeoffrey C Wall
Nov 12, 2009·The American Journal of Gastroenterology·Loren Laine, Charles Hennekens
Dec 3, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yumi NishiyaToshihiko Ikeda
Mar 17, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Katsunobu HagiharaToshihiko Ikeda
Oct 23, 2009·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Y NishiyaT Ikeda
Sep 9, 2017·Expert Opinion on Drug Metabolism & Toxicology·Samaneh SoleymaniMohammad Abdollahi
May 3, 2019·Pharmacology Research & Perspectives·Andrew S KuceyBrad L Urquhart
Mar 24, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Helinä KahmaJanne T Backman
Nov 16, 2021·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yongjie ZhangMiki Nakajima

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