{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T05:35:56Z","timestamp":1768714556641,"version":"3.49.0"},"reference-count":9,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2001,4,1]],"date-time":"2001-04-01T00:00:00Z","timestamp":986083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Furosemide (frusemide) is a weakly acidic diuretic drug. Its absorption is poor and variable, in part due to its restricted sites of absorption, mainly the stomach. The narrow absorption window of this drug can be explained by pH partition theory. The purpose of this study was to investigate the feasibility of widening the absorption window of furosemide by controlling the pH in distal portions of the gastrointestinal tract with officially used additives. Methacrylate copolymer (Eudragit L100\u201355), hydroxypropylmethylcellulose phthalate (HP-55) and hydroxypropylmethylcellulose acetate succinate (AS-MF) were selected as additives. The pH of suspensions of these additives was about 4, and the pH was adjusted to about 6\u20137 by the addition of NaOH. The Eudragit L100\u201355 suspension was found to be the most resistant to NaOH titration. When Eudragit L100\u201355 was used in an in-situ ileal loop experiment in rats, the pH of the intestinal contents was significantly reduced, from 7.9 \u00b1 0.1 to 5.7 \u00b1 0.1, and the plasma concentration of furosemide 15 min after administration was about 3 times higher than that in controls, 1.81 \u00b1 0.42 \u03bcg mL\u22121 vs 0.63 \u00b1 0.08 \u03bcg mL\u22121. However, the plasma concentration of [14C] mannitol was not changed by the co-administration of Eudragit L100\u201355. Furthermore, the AUC of furosemide was significantly increased by a factor of about 1.6 relative to that in controls by the co-administration of Eudragit L100\u201355, to 21.4 \u00b1 4.0 \u03bcg h mL\u22121 from 13.3 \u00b1 3.9 \u03bcg h mL\u22121, and the gastrointestinal pH in the midgut and ileum was significantly reduced, with most of the furosemide remaining in these segments at 2 h following the oral administration of furosemide with Eudragit L100\u201355 to rats. These findings clearly demonstrate that the addition of Eudragit L100\u201355 can increase the absorption of furosemide in distal portions of the gastrointestinal tract. In conclusion, it is feasible to widen the absorption window of furosemide by controlling the pH in distal portions of the gastrointestinal tract by the co-administration of Eudragit L100\u201355.<\/jats:p>","DOI":"10.1211\/0022357011775721","type":"journal-article","created":{"date-parts":[[2003,7,18]],"date-time":"2003-07-18T23:43:52Z","timestamp":1058571832000},"page":"433-440","source":"Crossref","is-referenced-by-count":29,"title":["Improvement in site-specific intestinal absorption of furosemide by Eudragit L100-55"],"prefix":"10.1093","volume":"53","author":[{"given":"T","family":"Terao","sequence":"first","affiliation":[{"name":"Formulation Research Institute, Otsuka Pharmaceutical Factory, Inc. , Naruto, Tokushima 772-8601,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Formulation Research Institute, Otsuka Pharmaceutical Factory, Inc. , Naruto, Tokushima 772-8601,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Shouji","sequence":"additional","affiliation":[{"name":"Formulation Research Institute, Otsuka Pharmaceutical Factory, Inc. , Naruto, Tokushima 772-8601,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,4,1]]},"reference":[{"key":"2024103110060055800_cit1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.2042-7158.1998.tb06171.x","article-title":"Evaluation of oral mucoadhesive microspheres in man on the basis of the pharmacokinetics of furosemide and riboflavin, compounds with limited gastrointestinal absorption sites","volume":"50","author":"Akiyama","year":"1998","journal-title":"J. Pharm. Pharmacol."},{"key":"2024103110060055800_cit2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF01059438","article-title":"Pharmacokinetics\/pharmacodynamics of furosemide in man: a review","volume":"7","author":"Benet","year":"1979","journal-title":"J. Pharmacokinet. Biopharm."},{"key":"2024103110060055800_cit3","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/BF01059061","article-title":"Evaluation of potential causes for the incomplete bioavailability of furosemide: gastric first-pass metabolism","volume":"11","author":"Lee","year":"1983","journal-title":"J. Pharmacokinet. Biopharm."},{"key":"2024103110060055800_cit4","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1098\/rspb.1988.0045","article-title":"The effect of Escherichia coli STa enterotoxin and other secretagogues on mucosal surface pH of rat small intestine in vivo","volume":"234","author":"McEwan","year":"1988","journal-title":"Proc. R. Soc. Lond. B. Biol. 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