Abstract
Signals from pharmacovigilance studies indicate that women are at higher risk for adverse drug reactions (ADRs) due to diuretics. Despite the long-term use of torasemide, there are few studies investigating gender differences of torasemide pharmacokinetics in the hospital setting. Therefore, torasemide pharmacokinetics were investigated in 90 patients (45 women, 45 men) during steady-state conditions. Torasemide elimination was significantly reduced in women compared with men (eg, body-weight-normalized area under the concentration-time curve: 42.1 +/- 20.4 vs 30.9 +/- 10.3 kg.h/L; P < .001). Among the investigated genetic factors [SLC22A11(OAT4), SLCO1B1(OATP1B1), CYP2C9], only the SLCO1B1c.521T>C polymorphism had a significant influence on torasemide pharmacokinetics. Using cell lines expressing OATP1B1, the authors identified torasemide as OATP1B1 substrate (K(m) = 6.2 microM) with a significant reduction of uptake by the 521C-variant. Taken together, gender differences in torasemide pharmacokinetics are likely to contribute to a higher rate of ADRs in women, which has, for example, been observed in a German Pharmacovigilance Project with 66% of hospitalizations due to torasemide ADRs occurring in women.
References
Dec 2, 1998·British Journal of Clinical Pharmacology·R M MartinR D Mann
May 10, 2000·Pharmacogenetics·J O MinersJ A Goldstein
Jan 5, 2002·American Journal of Clinical Dermatology·M Rademaker
Feb 16, 2002·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jorgelina A CerruttiAdriana M Torres
Jul 20, 2002·The Journal of Pharmacology and Experimental Therapeutics·Takashi NozawaTsuyoshi Yokoi
Dec 20, 2002·The Journal of Pharmacology and Experimental Therapeutics·Rommel G TironaRichard B Kim
Dec 20, 2003·Pharmacology·Anabel BrandoniAdriana M Torres
Dec 14, 2004·Clinical Pharmacology and Therapeutics·Stefan Viktor VormfeldeJürgen Brockmöller
Jun 11, 2005·Science·Jocelyn Kaiser
Mar 10, 2006·Naunyn-Schmiedeberg's Archives of Pharmacology·Jörg KönigMartin F Fromm
Apr 6, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Masaru HiranoYuichi Sugiyama
Aug 29, 2006·British Journal of Clinical Pharmacology·Stefan V VormfeldeJürgen Brockmöller
Sep 14, 2006·The Pharmacogenomics Journal·S V VormfeldeJ Brockmöller
May 15, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Alexander TreiberBruno Stieger
Sep 20, 2007·Therapeutische Umschau. Revue thérapeutique·Petra A Thürmann
Nov 29, 2007·Clinical Pharmacology and Therapeutics·S V VormfeldeJ Brockmöller
Mar 4, 2008·Diabetes·Iouri BachmakovJörg König
Mar 29, 2008·Expert Opinion on Drug Metabolism & Toxicology·Annick SeithelJörg König
Apr 11, 2008·Clinical Pharmacokinetics·Dierk WernerMartin F Fromm
Jun 14, 2008·Pharmacogenetics and Genomics·Stefan OswaldWerner Siegmund
Jul 8, 2008·European Journal of Clinical Pharmacology·Y ZopfH Dormann
Jul 25, 2008·The New England Journal of Medicine·UNKNOWN SEARCH Collaborative GroupR Collins
Citations
Feb 8, 2011·Drug Metabolism and Pharmacokinetics·Yoshihisa Shitara
Mar 16, 2011·Journal of Biomedicine & Biotechnology·Offie P SoldinDonald R Mattison
Dec 15, 2010·British Journal of Clinical Pharmacology·Eline M RodenburgLoes E Visser
May 8, 2015·European Heart Journal·Giuseppe M C RosanoJuan Tamargo
Oct 11, 2012·Drug Metabolism and Pharmacokinetics·Inna Y Gong, Richard B Kim
Mar 23, 2017·European Heart Journal. Cardiovascular Pharmacotherapy·J TamargoS Agewall
Feb 28, 2018·Clinical Cardiology·Evann EisenbergIleana L Piña
Feb 15, 2019·Current Heart Failure Reports·Richa GuptaSean Collins
Nov 22, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Saki IzumiYuichi Sugiyama
Jan 20, 2011·Pharmacological Reviews·Mikko NiemiPertti J Neuvonen
Feb 6, 2017·Clinical Science·Lea Gaignebet, Georgios Kararigas
Sep 23, 2018·Current Treatment Options in Cardiovascular Medicine·Daniela R Crousillat, Nasrien E Ibrahim
Oct 16, 2019·Cardiology Research and Practice·Tyler P RasmussenMilena A Gebska
Feb 2, 2021·Kardiologiia·V Yu MareevA I Chesnikova
Feb 2, 2021·Clinical Pharmacology and Therapeutics·Valérie CossonYuyan Jin
May 21, 2021·Advanced Drug Delivery Reviews·Christine M MadlaAbdul W Basit
Jul 20, 2021·Advanced Drug Delivery Reviews·José das NevesBruno Sarmento
May 17, 2021·Pharmacology & Therapeutics·Juan TamargoEva Delpón