Abstract
Not only the renal clearance but also the hepatic clearance of drugs varies with the progression of renal failure. The aim of this study was to investigate the effects of human uremic serum and various uremic toxins on the hepatic uptake of digoxin (DX), a drug mainly excreted into bile in patients with severe renal failure, using isolated rat and human hepatocytes as model systems. Uremic serum inhibited the uptake of DX into rat hepatocytes in a concentration-dependent manner, whereas normal serum did not affect the uptake. In addition, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), hippuric acid, indole-3-acetic acid, indoxyl sulfate, and p-cresol (PC) concentration dependently inhibited the uptake. CMPF and PC at the concentration of 400 microM, which is within the plasma concentration range attained in patients with renal failure, inhibited the uptake of DX into rat hepatocytes by 27% and 23%, respectively. In human hepatocytes, 10% uremic serum, 400 microM CMPF, and 400 microM PC inhibited the uptake of DX by 23.3%, 23.4%, and 28.2%, respectively. In conclusion, our results suggest that hepatic uptake of DX is likely to be inhibited by uremic toxins, such as CMPF and PC, present in the serum of patients with re...Continue Reading
References
Aug 1, 1978·Clinical Pharmacology and Therapeutics·A RaneR A Branch
Feb 1, 1985·Journal of Pharmacobio-dynamics·T MizumaS Awazu
Nov 1, 1981·Journal of Pharmacobio-dynamics·K YamaokaT Uno
Oct 1, 1995·Gastroenterology·G A Kullak-UblickP J Meier
Jun 1, 1997·Molecular Pharmacology·L ZhangK M Giacomini
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·B NoéP J Meier
Aug 15, 1998·Biochemical and Biophysical Research Communications·F Meyer-WentrupH Koepsell
Mar 27, 1999·FEBS Letters·M KakyoH Yawo
Jul 9, 1999·Pharmaceutical Research·Y TsutsumiM Otagiri
Aug 4, 1999·Journal of Chromatography. a·R De SmetR Vanholder
Dec 22, 1999·The Journal of Biological Chemistry·B HsiangT G Kirchgessner
Dec 23, 1999·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·G LesafferR Vanholder
Apr 26, 2000·The Journal of Biological Chemistry·J KönigD Keppler
Jun 6, 2000·FEBS Letters·V CattoriP J Meier
Aug 11, 2000·Kidney International. Supplement·A DhondtN Lameire
Oct 21, 2000·European Journal of Pharmacology·Z H HuangM Takano
Feb 13, 2001·Gastroenterology·G A Kullak-UblickB Hagenbuch
May 1, 2001·Biochemical and Biophysical Research Communications·W SunM D Erion
Jun 1, 2002·Journal of the American Society of Nephrology : JASN·Francois A LeblondVincent Pichette
Jul 24, 2002·Pharmaceutical Research·Takaaki KodawaraKen-ichi Inu
Jul 31, 2002·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Riccardo Maria FagugliRaymond Vanholder
Jan 22, 2003·Seminars in Dialysis·Albert W Dreisbach, Juan J L Lertora
Jan 23, 2003·The Journal of Pharmacology and Experimental Therapeutics·Yoshihisa ShitaraYuichi Sugiyama
Jan 25, 2003·The Journal of Pharmacy and Pharmacology·Su Yeon YuMyung Gull Lee
Mar 29, 2003·Physiological Reviews·Michael Trauner, James L Boyer
Apr 5, 2003·Kidney International·Raymond VanholderUNKNOWN European Uremic Toxin Work Group (EUTox)
Oct 9, 2003·Clinical Pharmacokinetics·Hans Lennernäs
Apr 30, 2004·Clinical Pharmacology and Therapeutics·Dennis W SchneckAli Raza
May 26, 2004·The Journal of Pharmacology and Experimental Therapeutics·Masaru HiranoYuichi Sugiyama
Jun 15, 2004·The Journal of Pharmacology and Experimental Therapeutics·Yoshihisa ShitaraYuichi Sugiyama
Jul 1, 2004·Pharmacogenetics·Mikko NiemiKari T Kivistö
Aug 3, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hong SunLeslie Z Benet
Dec 24, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Cuiping ChenTeresa A Smolarek
Jun 18, 2005·Clinical Pharmacology and Therapeutics·Mikko NiemiPertti J Neuvonen
Jul 5, 2005·The Journal of Pharmacology and Experimental Therapeutics·Lichuan LiuK Sandy Pang
Oct 4, 2005·Clinical Pharmacology and Therapeutics·Lauri I KajosaariJanne T Backman
Jun 20, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yi-an BiDavid B Duignan
Jan 27, 2007·Biopharmaceutics & Drug Disposition·Suwako ItoYasufumi Sawada
Citations
Aug 24, 2013·Toxins·Masayuki TsujimotoKohshi Nishiguchi
Sep 6, 2014·Toxins·Hitoshi UchiyamaKohshi Nishiguchi
May 28, 2011·Journal of Pharmaceutical Sciences·Maribel Reyes, Leslie Z Benet
May 4, 2011·Journal of Pharmaceutical Sciences·Hiroshi WatanabeToru Maruyama
Feb 19, 2015·Pharmacology Research & Perspectives·Hiroshi WatanabeToru Maruyama
Jan 18, 2013·Kidney International·Hiroshi WatanabeToru Maruyama
Oct 18, 2013·Kidney International·Catherine K YeungJonathan Himmelfarb
Jun 2, 2015·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yuichi IchimuraHiroshi Saitoh
Jul 4, 2015·Clinical Pharmacokinetics·Frederique RodieuxMarc Pfister
Nov 30, 2012·Therapeutic Apheresis and Dialysis : Official Peer-reviewed Journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy·Masayuki TsujimotoKohshi Nishiguchi
Jan 18, 2012·Journal of Clinical Pharmacology·Judith NaudVincent Pichette
Aug 21, 2010·The Journal of Pharmacy and Pharmacology·Masayuki TsujimotoKohshi Nishiguchi
Oct 15, 2013·Therapeutic Apheresis and Dialysis : Official Peer-reviewed Journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy·Masayuki TsujimotoKohshi Nishiguchi
Apr 12, 2015·Néphrologie & thérapeutique·Judith NaudVincent Pichette
Jan 11, 2018·Toxins·Raymond VanholderGriet Glorieux
Oct 13, 2017·Therapeutic Apheresis and Dialysis : Official Peer-reviewed Journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy·Piotr Jan NowakMichal Nowicki
Sep 15, 2017·Expert Review of Clinical Pharmacology·Alexander J Prokopienko, Thomas D Nolin
Dec 30, 2017·Clinical Pharmacology and Therapeutics·David MartinezChantal Barin-Le Guellec
Jun 21, 2015·Pharmacological Reviews·Dustin R WalshPeter A Friedman
Oct 24, 2014·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Jennifer C RyanBrian S Decker
Sep 17, 2020·Toxins·Amanda L Graboski, Matthew R Redinbo
Sep 9, 2009·Upsala Journal of Medical Sciences·Marta Vazquez-HernandezJ Carlos Tutor
Aug 29, 2016·European Journal of Clinical Pharmacology·Willemijn L EppengaPeter A G M De Smet
Apr 26, 2018·Cancer Chemotherapy and Pharmacology·Hiroyoshi KoideKohshi Nishiguchi
Oct 31, 2019·Scientific Reports·Shoichi OzawaKohshi Nishiguchi