title: GI drug absorption in rats exposed to cobalt-60 gamma-radiation II: in vivo rate of absorption.
abstract: The rate of absorption of sulfanilamide, bretylium tosylate, sulfisoxazole acetyl, and riboflavin was studied in rats exposed to 850 rad of cobalt-60 gamma-radiation either 1 or 5 days before oral drug administration. Polyethylene glycol 4000 was administered with sulfanilamide; its distribution along the GI tract indicated that the gastric emptying rate was reduced threefold at 1 day postirradiation but returned to normal at 5 days postirradiation; the small intestinal transit rate was not detectably altered by irradiation. At 1 day postirradiation, there was a marked decrease in the absorption rate of sulfanilamide, a smaller, although significant, decrease in the absorption rate of sulfisoxazole acetyl and bretylium, and an increase in the absorption rate of riboflavin. At 5 days postirradiation, the drug absorption rate was normal. The changes in the absorption rate of the drugs were due to a radiation-induced reduction in the gastric emptying rate; the permeability of the GI epithelium did not appear to be affected by radiation. The results indicate that, immediately following irradiation, a marked reduction in the gastric emptying rate causes a pronounced reduction in the absorption rate of rapidly absorbed drugs, a less pronounced reduction in the absorption rate of drugs that are absorbed slowly because of slow dissolution or slow diffusion across the GI epithelium, and an increase in the absorption rate of drugs that are absorbed by a saturable mechanism provided the mechanism is not impaired by irradiation.
mesh_terms: D000818:Animals; D001950:Bretylium Tosylate / Q000097:blood / Q000378:metabolism; D003037:Cobalt Radioisotopes; D005720:Gamma Rays; D005753:Gastric Mucosa / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000528:radiation effects; D007408:Intestinal Absorption / Q000528:radiation effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D011092:Polyethylene Glycols; D051381:Rats; D012256:Riboflavin / Q000097:blood / Q000378:metabolism; D013424:Sulfanilamides / Q000097:blood / Q000378:metabolism; D013444:Sulfisoxazole / Q000097:blood / Q000378:metabolism; D013997:Time Factors
chemical_list: D003037:Cobalt Radioisotopes; D013424:Sulfanilamides; D011092:Polyethylene Glycols; D013444:Sulfisoxazole; D001950:Bretylium Tosylate; D012256:Riboflavin