Increasing systemic exposure of methotrexate by active efflux mediated by multidrug resistance-associated protein 3 (mrp3/abcc3)

The Journal of Pharmacology and Experimental Therapeutics
Yoshiaki KitamuraYuichi Sugiyama

Abstract

The aim of this study was to investigate the functional importance of multidrug resistance-associated protein (Mrp)3/Abcc3 and Mrp4/Abcc4 in the pharmacokinetics of methotrexate. Compared with the corresponding wild-type mice, the plasma concentrations of methotrexate given orally were similar in Abcc4(-/-) mice and were significantly lower in Abcc3(-/-) mice. Pharmacokinetic parameters related to hepatobiliary transport were determined under steady-state conditions in wild-type and Abcc3(-/-) mice that were given a constant intravenous infusion of methotrexate. The biliary clearance, based on the plasma concentration, was 1.6-fold greater in Abcc3(-/-) mice than in wild-type mice (23 and 15 ml/min/kg, respectively, P < 0.05). Because the basolateral uptake and canalicular efflux clearances of methotrexate were similar in wild-type and Abcc3(-/-) mice, this result suggests that the basolateral efflux clearance of methotrexate is decreased in the liver of Abcc3(-/-) mice. Furthermore, a lower fraction of absorption of methotrexate (F(a) F(g)) was suggested in Abcc3(-/-) mice (0.49 and 0.29 in wild-type and Abcc3(-/-) mice, respectively). The mucosal-to-serosal transport rate of methotrexate, determined in vitro using everted sac...Continue Reading

References

Jan 1, 1978·Clinical Pharmacokinetics·D D Shen, D L Azarnoff
Jul 1, 1995·The American Journal of Physiology·T KuwabaraY Sugiyama
Jul 1, 1993·Pharmaceutical Research·B Davies, T Morris
Jul 1, 1997·Toxicology and Industrial Health·R P BrownR P Beliles
Feb 10, 1999·Clinical Pharmacology and Therapeutics·L J EganJ J Lipsky
May 18, 1999·The Journal of Biological Chemistry·T HirohashiY Sugiyama
Feb 19, 2002·Laboratory Investigation; a Journal of Technical Methods and Pathology·George L SchefferRik J Scheper
Feb 22, 2002·Journal of the American Society of Nephrology : JASN·Rémon A M H van AubelFrans G M Russel
Mar 19, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·Daniel RostWolfgang Stremmel
Jan 21, 2004·Journal of Gastroenterology and Hepatology·Makoto KurodaYukihiko Adachi
Jun 26, 2004·American Journal of Physiology. Gastrointestinal and Liver Physiology·Takahiro ShojiYuichi Sugiyama
Aug 18, 2004·Molecular and Cellular Biology·Markos LeggasJohn D Schuetz
Apr 9, 2005·Molecular Pharmacology·Martin G BelinskyGary D Kruh
May 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Noam ZelcerPiet Borst
Oct 27, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·José E ManautouRonald Oude Elferink
Apr 6, 2006·Pflügers Archiv : European journal of physiology·Piet BorstKoen van de Wetering
Apr 14, 2006·The Journal of Pharmacology and Experimental Therapeutics·M L H VlamingA H Schinkel
Apr 22, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Albert MennoneJames L Boyer
Mar 14, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Junichi EnokizonoYuichi Sugiyama
Jun 21, 2007·The Journal of Pharmacology and Experimental Therapeutics·Yoshitane NozakiYuichi Sugiyama
Feb 5, 2008·Molecular Pharmacology·Soichiro MatsushimaYuichi Sugiyama

❮ Previous
Next ❯

Citations

Feb 15, 2011·Pharmacogenetics and Genomics·Torben S MikkelsenRuss B Altman
May 23, 2013·Clinical and Experimental Pharmacology & Physiology·Jian-Jun ZouHong-Guang Xie
Aug 16, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Zhan WangJames M Gallo
Dec 3, 2009·Biological & Pharmaceutical Bulletin·Eva BrcakovaStanislav Micuda
Apr 23, 2011·Drug Metabolism and Pharmacokinetics·Tomohiro SasakiIchiro Ieiri
Feb 12, 2014·Annual Review of Physiology·Michele VisentinI David Goldman
Oct 9, 2012·Advanced Drug Delivery Reviews·Margarida EstudanteLeslie Z Benet
May 17, 2011·Annual Review of Nutrition·Rongbao ZhaoI David Goldman
Aug 2, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Rhiannon N HardwickNathan J Cherrington
Nov 9, 2014·Expert Opinion on Drug Metabolism & Toxicology·Lori W E van der SchoorJohan W Jonker
Dec 16, 2011·Biopharmaceutics & Drug Disposition·Marilyn E MorrisLisa J Benincosa
Jan 20, 2015·Biopharmaceutics & Drug Disposition·Yu-Qin PanHong-Guang Xie
Mar 31, 2012·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Jason A SprowlAlex Sparreboom
Sep 12, 2013·Current Opinion in Pharmacology·Seng Chuan TangAlfred H Schinkel
Nov 29, 2013·Drug Metabolism and Pharmacokinetics·Katsuhisa Inoue, Hiroaki Yuasa
Mar 3, 2009·Drug Metabolism and Pharmacokinetics·Hiroyuki Kusuhara, Yuichi Sugiyama
Jul 9, 2010·Drug Metabolism and Pharmacokinetics·Tomoya Narawa, Tomoo Itoh
Jun 5, 2014·Psychopharmacology·R SeigersS B Schagen
Sep 3, 2016·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Lu XiaoHua Zhou
May 24, 2016·Fundamental & Clinical Pharmacology·Azza A K El-SheikhAbdulla Y Al-Taher
Apr 12, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mariline GameiroFernando Remião
Nov 24, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yuichi Uwai
Feb 24, 2018·Current Medicinal Chemistry·Carolina I Ghanem, Jose E Manautou
Dec 3, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jin-Zi JiHong-Guang Xie
Jan 28, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ramola SaneJames M Gallo
Apr 15, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tomoko WatanabeYuichi Sugiyama
Aug 16, 2016·Journal of Cardiovascular Pharmacology·Ting TaiHong-Guang Xie
Jun 25, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Brian D FurmanskiSharyn D Baker
Nov 13, 2020·Journal of Acquired Immune Deficiency Syndromes : JAIDS·David GingrichUNKNOWN ACTG 5314 Protocol Team

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

© 2022 Meta ULC. All rights reserved