Effects of colestipol hydrochloride on drug absorption in the rat II.

The effects of colestipol hydrochloride, a hypocholesterolemic bile acid-binding anion-exchange polymer, on the GI absorption of drugs commonly used in humans were studied in the rat. Colestipol hydrochloride was given by gavage in single doses of 71.5 or 214.5 mg/kg, equivalent to 5 or 15 g, respectively, in a 70-kg human; controls received equivalent amounts of microcrystalline cellulose. Single oral doses of labeled drugs were given concurrently with colestipol hydrochloride or microcrystalline cellulose at the human therapeutic dose range on a milligrams per kilogram basis. Subsequent changes in serum drug levels were measured at several time periods, and absorption was evaluated as the total area under the time-concentration curve. Colestipol hydrochloride at either dose did not significantly alter the absorption of 6-14C-nicotinic acid, 7-3H-tetracycline, 35S-chlorpromazine, 12alpha-3H-digoxin, warfarin (alpha-14C-benzyl), or clofibrate (14C-carboxyl). In addition, the effects of 214.5 mg/kg of colestipol hydrochloride were compared with the same dose of cholestyramine with respect to the absorption of 3-14C-hydrochlorothiazide, 2-14C-phenobarbital, and 3H-digitoxin. Cholestyramine reduced absorption of hydrochlorothiazide by 42%, but colestipol hydrochloride had no significant effect. Neither resin altered phenobarbital or digitoxin absorption when compared with the the control, but a significant difference occurred between the two resins with digitoxin; areas under the time-concentration curve [in (dpm/0.1 ml serum) x hr] were: colestipol hydrochloride, 2001; cholestyramine, 16,300; and cellulose, 17, 067. These results indicate that colestipol hydrochloride and cholestyramine can differ in their effects on the absorption of certain drugs from the GI tract of the rat.