title: Absorption, distribution and excretion of GT31-104, a novel bile acid sequestrant, in rats and dogs after acute and subchronic administration.
abstract: The absorption, distribution, and excretion of GT31-104, a novel bile acid sequestrant, was studied in rats and dogs after both acute and subchronic oral administration. The polyallylamine backbone of GT31-104 was labeled with tritium and one of the alkyl side chains was labeled with 14C. The mean blood and plasma concentration of [3H, 14C]GT31-104 in rats, in both treatment regimens, was negligible at all time points, with the highest amount observed being 0.69 microgram eq/g blood; in dogs the mean blood and plasma concentration of [3H, 14C]GT31-104 was below the limit of quantitation (< 0.001% total dose) at all time points. In both rats and dogs, the mean total urinary excretion of [3H, 14C]GT31-104 was approximately 0.06% of the total dose. The fecal excretion data indicates that both 3H- and 14C-derived radioactivity was excreted entirely in the feces. Mean total radioactivity excreted in the feces ranged from approximately 95 to 105% in the rats and 92 to 102% in the dogs. Across the different treatment regimens, in both species, tissue concentrations were negligible (< 0.01% total dose) and no differences in tissue profile were noted, indicating that there was no effect of pretreatment on [3H, 14C]GT31-104 absorption. GT31-104 was extracted with water, and the water-soluble portion contained radioactivity that would correlate to approximately 0.19% of the 3H dose and 0.41% of the 14C dose; this portion probably accounted for the negligible radioactivity observed systemically. Analysis of gastrointestinal (GI) tract tissues with contents indicated that GT31-104 is rapidly cleared from the GI tract. These data indicate that GT31-104 is not absorbed from the GI tract in rats and dogs.
authors.affiliation: GelTex Pharmaceuticals, Inc., Waltham, MA 02154, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Rosenbaum
authors.forename: J S
authors.initials: JS
authors.lastname: Petersen
authors.forename: S
authors.initials: S
authors.lastname: Ducharme
authors.forename: P
authors.initials: P
authors.lastname: Markham
authors.forename: D I
authors.initials: DI
authors.lastname: Goldberg
mesh_terms: D000499:Allylamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000069472:Colesevelam Hydrochloride; D004064:Digestive System / Q000378:metabolism; D004285:Dogs; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002756:Cholagogues and Choleretics; D000499:Allylamine; D000069472:Colesevelam Hydrochloride