Abstract
The effect of dotinurad [(3,5-dichloro-4-hydroxyphenyl)(1,1-dioxo-1,2-dihydro-3H-1λ6-1,3-benzothiazol-3-yl)methanone] was compared with that of commercially available uricosuric agents-namely, benzbromarone, lesinurad, and probenecid. Its effect on urate secretion transporters was evaluated using probe substrates for respective transporters. Dotinurad, benzbromarone, lesinurad, and probenecid inhibited urate transporter 1 (URAT1) with IC50 values of 0.0372, 0.190, 30.0, and 165 μM, respectively. Dotinurad weakly inhibited ATP-binding cassette subfamily G member 2 (ABCG2), organic anion transporter 1 (OAT1), and OAT3, with IC50 values of 4.16, 4.08, and 1.32 μM, respectively, indicating higher selectivity for URAT1. The hypouricemic effects of dotinurad and benzbromarone were evaluated in Cebus monkeys. Dotinurad, at doses of 1-30 mg/kg, concomitantly decreased plasma urate levels and increased fractional excretion of urate (FEUA) in a dose-dependent manner. On the contrary, benzbromarone, at a dose of 30 mg/kg, showed a modest effect on plasma urate levels. The inhibitory effect of dotinurad on urate secretion transporters was evaluated in Sprague-Dawley rats, with sulfasalazine and adefovir as probe substrates of ABCG2 and OAT...Continue Reading
References
Dec 1, 1967·Annals of Internal Medicine·T Yü, A B Gutman
Dec 1, 1980·Japanese Journal of Pharmacology·Y YonetaniK Iwaki
Nov 1, 1995·Antimicrobial Agents and Chemotherapy·K C CundyH S Jaffe
Jan 1, 1996·Antimicrobial Agents and Chemotherapy·L NaesensE De Clercq
May 25, 2002·Nature·Atsushi EnomotoHitoshi Endou
Dec 11, 2002·Kidney International·Kimiyoshi IchidaHitoshi Endou
Jan 30, 2003·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Vincent JullienElisabeth Rey
Jul 19, 2008·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Ming-Han H LeeRichard O Day
Sep 19, 2008·Journal of the American Society of Nephrology : JASN·Rudolf P ObermayrRenate Klauser-Braun
Jun 23, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Arik Dahan, Gordon L Amidon
Nov 21, 2009·Journal of the American Society of Nephrology : JASN·Dganit DinourEliezer J Holtzman
Jan 5, 2010·Nature Reviews. Rheumatology·Robert Terkeltaub
Mar 2, 2010·Biological & Pharmaceutical Bulletin·Masanobu SatoIkumi Tamai
Apr 7, 2010·Science Translational Medicine·Hirotaka MatsuoNariyoshi Shinomiya
Oct 19, 2010·The Journal of Pharmacology and Experimental Therapeutics·Koji MatsumotoTakeshi Nishino
Jan 29, 2011·Nephrology·Ho Jung ShinHitoshi Endou
Feb 4, 2011·The New England Journal of Medicine·Tuhina Neogi
Feb 22, 2012·PloS One·Atsushi HosomiIkumi Tamai
Apr 5, 2012·Nature Communications·Kimiyoshi IchidaHiroshi Suzuki
Apr 22, 2014·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Kazuya MaedaYuichi Sugiyama
Apr 16, 2015·British Journal of Clinical Pharmacology·Keisuke GotandaIchiro Ieiri
Jul 8, 2015·Nature Reviews. Rheumatology·Chang-Fu KuoMichael Doherty
Nov 22, 2015·The Journal of Pharmacy and Pharmacology·Tetsuya TaniguchiKazuhiro Saitoh
Feb 26, 2016·The Journal of Pharmacology and Experimental Therapeutics·Sung Oh AhnNaoshi Horiba
Mar 16, 2016·Metabolism: Clinical and Experimental·Tae Yang YuJae Hyeon Kim
Jun 9, 2016·Clinical Kidney Journal·Vibha BhatnagarSanjay K Nigam
Oct 8, 2016·Arthritis Research & Therapy·Jeffrey N MinerBarry Quart
Dec 10, 2016·Naunyn-Schmiedeberg's Archives of Pharmacology·Tetsuya TaniguchiTakashi Iwanaga
Jan 14, 2017·Frontiers in Pharmacology·Hiroshi MiyataHiroshi Suzuki
Jul 12, 2017·Scientific Reports·Wei WuSanjay K Nigam
May 31, 2018·Current Opinion in Nephrology and Hypertension·Sanjay K Nigam, Vibha Bhatnagar
Jun 9, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Rachel E KosaManthena V Varma
Citations
Nov 23, 2019·Clinical and Experimental Nephrology·Tatsuo HosoyaTetsuo Ohashi
Apr 25, 2020·Expert Opinion on Drug Discovery·Naoyuki OtaniNaohiko Anzai
Dec 4, 2019·Pharmacology Research & Perspectives·Keisuke MotokiTetsuo Ohashi
Jan 1, 2020·Clinical and Experimental Nephrology·Hiroshi NakataniTetsuo Ohashi
Feb 19, 2020·Clinical and Experimental Nephrology·Tatsuo HosoyaShingo Kanda
Jan 24, 2020·Clinical and Experimental Nephrology·Tatsuo HosoyaShingo Kanda
Nov 18, 2019·Clinical and Experimental Nephrology·Daisuke OkuiTetsuo Ohashi
Dec 27, 2019·Clinical and Experimental Nephrology·Tatsuo HosoyaTetsuo Ohashi
Dec 4, 2019·Clinical and Experimental Nephrology·Tatsuo HosoyaTetsuo Ohashi
Jan 26, 2020·Clinical and Experimental Nephrology·Tatsuo HosoyaTetsuo Ohashi
Feb 23, 2020·Clinical and Experimental Nephrology·Kenichi FurihataYuji Kumagai
Jun 4, 2020·Nutrients·Hiroki SaitoHiroshi Suzuki
Nov 3, 2020·Biological & Pharmaceutical Bulletin·Hiroshi ArakawaIkumi Tamai
Nov 3, 2020·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Tetsuya Taniguchi, Naoki Ashizawa
Feb 20, 2021·Journal of Pharmaceutical Sciences·Azusa FutatsugiYukio Kato
Mar 27, 2021·Acta Pharmacologica Sinica·Ze-An ZhaoJian-Xin Pang
Apr 2, 2021·Scientific Reports·Tetsuya TaniguchiTakashi Iwanaga
Apr 10, 2021·Drug Metabolism and Pharmacokinetics·Heng Lin TanEric Chun Yong Chan
May 1, 2021·Expert Opinion on Pharmacotherapy·Tomohiko IshikawaTatsuo Hosoya
May 18, 2021·Curēus·Ayman IqbalMehreen Malik
Jul 3, 2021·Pharmaceutics·Péter TátraiPéter Krajcsi
Aug 24, 2021·Clinical and Experimental Hypertension : CHE·Toshinari TakahashiTatsuo Hosoya
Sep 12, 2021·European Heart Journal·Eun Ha KangSeoyoung C Kim
Aug 13, 2021·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Koichi OmuraTakashi Iwanaga