{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T00:29:03Z","timestamp":1700267343366},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,1,16]],"date-time":"2006-01-16T00:00:00Z","timestamp":1137369600000},"content-version":"vor","delay-in-days":4308,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[1994,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The pharmacokinetics and pharmacodynamics of furosemide were investigated after intravenous (i.v.), 1 mg\/100 g body weight, and oral administration, 2 mg per 100g body weight, to spontaneously hypertensive rats (SHRs) and deoxycorticosterone acetate\u2010salt\u2010induced hypertensive rats (DOCA\u2010salt rats). After i.v. administration, the 8 h urinary excretion of furosemide\/g kidney (397 versus 572 \u03bcg) was significantly lower and the non\u2010renal clearance (5.78 versus 3\u00b794 ml min<jats:sup>\u22121<\/jats:sup> kg<jats:sup>\u22121<\/jats:sup>) was significantly faster in SHRs of 16 weeks of age than in age\u2010matched control Wistar rats. This suggested that the nonrenal metabolism of furosemide could be faster in SHRs of 16 weeks of age than in age\u2010matched control Wistar rats, and this could be supported by the significantly greater amount of 4\u2010chloro\u20105\u2010sulphamoyl anthranilic acid, a metabolite of furosemide, excreted in 8 h urine as expressed in terms of furosemide (11\u00b71 versus 4\u00b779% of the i.v. dose) in SHRs. It could also be supported at least in part by a study of liver homogenate; the amount of furosemide remaining per gram of liver after 30 min incubation of 50\u03bcg of furosemide with the 9000g supernatant fraction of liver homogenate was significantly smaller (40\u00b74 versus 43\u00b77\u03bcg) in SHRs of 16 weeks of age than in age\u2010matched Wistar rats. The greater metabolic activity of furosemide in liver may also be supported by the result that the amount of hepatic cytochrome P\u2010450 (0\u00b77013 versus 0\u00b75186 nmol\/mg protein) and the weights of liver (3\u00b752 versus 2\u00b793% of body weight) were significantly greater in SHRs of 16 weeks of age than in age\u2010matched Wistar rats. After i.v. administration of furosemide, the 8 h urine output (9\u00b793 versus 16\u00b75 ml) and 8 h urinary excretion of sodium (1\u00b721 versus 2\u00b705 mmol) and chloride (1\u00b737 versus 2\u00b717 mmol) per gram of kidney in SHRs of 16 weeks of age were lower than those in age\u2010matched Wistar rats, this could be due to the significantly smaller amount of furosemide excreted in 8 h urine per gram of kidney. After oral administration, the pharmacokinetics and pharmacodynamics of furosemide were not significantly different between SHRs and the control Wistar rats of 16 weeks of age. After i.v. and oral administration of furosemide, there were no significant differences in the pharmacokinetics and pharmacodynamics between DOCA\u2010salt rats and control SD rats of 16 weeks of age except for the significantly lower urinary excretion of potassium per gram of kidney in DOCA\u2010salt rats. On the other hand, the 8 h urinary excretion of furosemide and non\u2010renal clearance were not significantly different between SHRs of six weeks of age and age\u2010matched control Wistar rats after i.v. administration of furosemide. Since the non\u2010renal metabolism of furosemide was not faster in either DOCA\u2010salt rats of 16 weeks of age or SHRs of six weeks of age than that in the respective age\u2010matched control group, the faster non\u2010renal metabolism of furosemide in SHRs of 16 weeks of age could be due to the physiological factor from the chronic phase of hypertension in SHRs, and could not be due solely to the heredity of SHRs or the hypertensive state itself.<\/jats:p>","DOI":"10.1002\/bdd.2510150302","type":"journal-article","created":{"date-parts":[[2006,10,14]],"date-time":"2006-10-14T09:36:08Z","timestamp":1160818568000},"page":"185-206","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacokinetics and pharmacodynamics of furosemide after intravenous and oral administration to spontaneously hypertensive rats and DOCA\u2010salt\u2010induced hypertensive rats"],"prefix":"10.1002","volume":"15","author":[{"given":"Seong H.","family":"Jang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myung G.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nak D.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,1,16]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01059086"},{"key":"e_1_2_1_3_2","first-page":"381","article-title":"Furosemide (Frusemide). 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