{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T19:38:16Z","timestamp":1757705896815},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,12,23]],"date-time":"2002-12-23T00:00:00Z","timestamp":1040601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2003,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The importance of plasma protein binding of intravenous furosemide in circulating blood for its urinary excretion and hence its diuretic effects in mutant Nagase analbuminemic rats (NARs, an animal model for human familial analbuminemia) was reported. Based on the furosemide report, the diuretic effects of another loop diuretic, torasemide, could be expected in NARs if plasma protein binding of torasemide is considerable in the rats. This was proven by this study. After intravenous administration of torasemide, 10 mg\/kg, to NARs, the plasma protein binding of torasemide was 23.3% in the rats due to binding to <jats:italic>\u03b1<\/jats:italic>\u2010 and <jats:italic>\u03b2<\/jats:italic>\u2010globulins (this value, 23.3%, was greater than only 12% for furosemide), and hence the percentages of intravenous dose of torasemide excreted in 8\u2010h urine as unchanged drug was 14.9% in the rat (this value was considerably greater than only 7% for furosemide). After intravenous administration of torasemide to NARs, the AUC (301 versus 2680 \u00b5g\/min\/ml) was significantly smaller [due to significantly faster both Cl<jats:sub>r<\/jats:sub> (4.81 versus 0.386 ml\/min\/kg) and Cl<jats:sub>nr<\/jats:sub> (28.3 versus 3.33 ml\/min\/kg)], terminal half\u2010life (18.3 versus 73.5 min) and mean residence time (6.97 versus 61.8 min) were significantly shorter (due to faster Cl, 33.2 versus 3.74 ml\/min\/kg), and amount of 8\u2010h urinary excretion of unchanged torasemide (446 versus 323 \u00b5g, due to increase in intrinsic renal excretion) was significantly greater than those in control rats. The 8\u2010h urine output and 8\u2010h urinary excretions of sodium and chloride were comparable between two groups of rats although the 8\u2010h urinary excretion of torasemide was significantly greater in NARs. This could be explained by the following. The amount of urinary excretion of torasemide was significantly greater in NARs than that in control rats only between 0 and 30 min urine collection. In both groups of rats, the urinary excretion rate of torasemide during 0\u201330 min reached an upper plateau with respect to urine flow rate as well urinary excretion rates of sodium and chloride. Therefore, the diuretic effects (8\u2010h urine output and 8\u2010h urinary excretions of sodium and chloride) were not significantly different between the two groups of rats. Copyright \u00a9 2002 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.333","type":"journal-article","created":{"date-parts":[[2003,1,7]],"date-time":"2003-01-07T21:14:01Z","timestamp":1041974041000},"page":"27-35","source":"Crossref","is-referenced-by-count":17,"title":["Pharmacokinetics and pharmacodynamics of intravenous trasemide in mutant nagase aalbuminemic rats"],"prefix":"10.1002","volume":"24","author":[{"given":"Eun J.","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myung G.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,12,23]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1987.192"},{"key":"e_1_2_1_3_2","first-page":"484","article-title":"Renal secretion of phenolsulphonphthalein: Analysis of its vectorial transport in normal and mutant analbuminemic rats","volume":"105","author":"Inoue M","year":"1985","journal-title":"J Lab Clin Med"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1985.tb09007.x"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.267"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199834010-00001"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199100413-00003"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00541462"},{"key":"e_1_2_1_9_2","first-page":"1527","article-title":"Renal effects of the high ceiling diuretic torasemide in rats and dogs","volume":"35","author":"Ghys BA","year":"1985","journal-title":"Arzneim\u2010Forsch\/Drug Res"},{"key":"e_1_2_1_10_2","first-page":"1532","article-title":"Renal effects of torasemide in rat","volume":"35","author":"Hermes BH","year":"1985","journal-title":"Arzneim\u2010Forsch\/Drug Res"},{"key":"e_1_2_1_11_2","first-page":"1520","article-title":"Pharmacological properties of the new potent diuretic torasemide in rats and dogs","volume":"35","author":"Ghys BA","year":"1985","journal-title":"Arzneim\u2010Forsch\/Drug Res"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0731-7085(87)80029-8"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-081X(199710)18:7<595::AID-BDD44>3.0.CO;2-F"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2710.1991.tb00337.x"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600710316"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1201\/b14095"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01062108"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01061772"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600690125"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600680843"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01061729"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1538\/expanim1978.29.1_33"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018943613122"},{"key":"e_1_2_1_24_2","first-page":"1536","article-title":"Effects of the diuretic torasemide on p\u2010aminohippuric acid transport in the rats","volume":"35","author":"Kramp RA","year":"1985","journal-title":"Arzneim\u2010Forsch\/Drug Res"},{"key":"e_1_2_1_25_2","volume-title":"Clinical Biochemical and Hematological Reference Values in Normal Experimental Animals and Normal Humans","author":"Mitruka BM","year":"1981"},{"key":"e_1_2_1_26_2","first-page":"1076","article-title":"Human hepatic cytochrome P450 2C9 catalyzes the rate\u2010limiting pathway of torasemide metabolism","volume":"272","author":"Miners JO","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.451621"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00018.x"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1159\/000176469"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(96)80207-8"},{"key":"e_1_2_1_31_2","first-page":"109","article-title":"Comparison between torasemide and furosemide in the treatment of ascites in cirrhotic patients","volume":"88","author":"Marelli A","year":"1997","journal-title":"Minerva Med"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1080\/003655201750074672"}],"container-title":["Biopharmaceutics &amp; 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