{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T09:58:18Z","timestamp":1777111098876,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,4,21]],"date-time":"2006-04-21T00:00:00Z","timestamp":1145577600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate the association between torsemide renal clearance and genetic variation in the basolaterally expressed renal organic anion transporters OAT1 and OAT3 and in the luminally situated OAT4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analysed 22 polymorphisms in the OAT coding genes <jats:italic>SLC22A6<\/jats:italic>, <jats:italic>SLC22A8<\/jats:italic> and <jats:italic>SLC22A11<\/jats:italic> and their haplotypes and measured torsemide renal clearance in 95 healthy men. In addition, the effect of torsemide on the OAT\u2010mediated transport was studied <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In stably transfected HEK293 cells torsemide (100\u2003\u00b5<jats:sc>m<\/jats:sc>) inhibited the uptake by human OAT1, OAT3 and OAT4 by 63.1, 58.1 and 68.0%, respectively. Torsemide renal clearance ranged from 6.5 to 43.1\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup> with a log\u2010normal distribution and a geometric mean of 15.6\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup> (15.0\u201316.1\u2003\u00b1\u2003SEM). No clear outlier group was observed. AA carriers of the polymorphism rs11231809 in <jats:italic>SLC22A11<\/jats:italic>\u2003had a torsemide renal clearance of 13.3\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup> (12.7\u201313.9) compared with 15.1\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup> (14.5\u201315.8) in AT and 18.0\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup> (16.7\u201319.5) in TT carriers (<jats:italic>P\u2003<\/jats:italic>=\u20030.002). The two most frequent haplotypes at <jats:italic>SLC22A11<\/jats:italic> showed an association with torsemide renal clearance. Homozygous carriage of these two haplotypes resulted in renal clearances of 21.2\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup> (19.0\u201323.7) and 11.8\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup> (10.5\u201313.5), respectively. No association between reanl clearance and genetic variation in <jats:italic>SLC22A6<\/jats:italic> or <jats:italic>SLC22A8<\/jats:italic> was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Genetic variation in the gene encoding the luminally expressed OAT4 rather than in the basolaterally expressed OATs may affect the renal clearance of torsemide.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2006.02655.x","type":"journal-article","created":{"date-parts":[[2006,4,21]],"date-time":"2006-04-21T22:45:50Z","timestamp":1145659550000},"page":"323-335","source":"Crossref","is-referenced-by-count":53,"title":["Torsemide renal clearance and genetic variation in luminal and basolateral organic anion transporters"],"prefix":"10.1111","volume":"62","author":[{"given":"Stefan V.","family":"Vormfelde","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Schirmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohannes","family":"Hagos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad R.","family":"Toliat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Engelhardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingolf","family":"Meineke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard","family":"Burckhardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"N\u00fcrnberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Brockm\u00f6ller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,4,21]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.55.3.1"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389200033489460"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-003-1192-y"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0730857100"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-003-1089-9"},{"key":"e_1_2_6_7_2","first-page":"114","article-title":"Molecular physiology of renal p\u2010aminohippurate secretion","volume":"16","author":"Burckhardt G","year":"2001","journal-title":"News Physiol Sci"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2004.10.006"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1517\/phgs.4.6.701.22817"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10254-002-0003-8"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00040.2003"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.059139"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1159\/000176466"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2004.08.024"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s100380170019"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.084301"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1488"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/01213011-200504000-00003"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(03)00060-2"},{"key":"e_1_2_6_20_2","article-title":"Uptake of chemically reactive, DNA\u2010damaging sulfuric esters into renal cells by human organic anion transporters","author":"Bakhiya N","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2005.11.013"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth457"},{"key":"e_1_2_6_23_2","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1093\/genetics\/50.4.757","article-title":"The Interaction of selection and linkage. 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