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 L100-55), 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 6-7 by the addition of NaOH. The Eudragit L100-55 suspension was found to be the most resistant to NaOH titration. When Eudragit L100-55 was used in an in-situ ileal loop experiment in rats, the pH of the intestinal contents was significantly reduced, from 7.9+/-0.1 to 5.7+/-0.1, and the plasma concentration of furosemide 15 min after administration was about 3 times higher than that in controls, 1.81+/- 0.42microg mL(-1) vs 0.63+/-0.08 microg mL(-1). However, the plasma concentration of [14C] mannitol was not changed by the co-administration of Eudragit L100-55. 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 L100-55, to 21.4+/-4.0 microg h mL(-1) from 13.3+/- 3.9 microg h mL(-1), 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 L100-55 to rats. These findings clearly demonstrate that the addition of Eudragit L100-55 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 L100-55.