Gastrointestinal drug absorption in rats exposed to 60Co γ-radiation

Following exposure of the gastrointestinal (GI) tract to ionizing radiation, its structure and function are altered for several days. Such alterations may affect the bioavailability of orally administered drugs. The potential mechanisms by which radiation may affect drug absorption were explored by studying the absorption of four test drugs, sulfanilamide, bretylium, sulfisoxazole acetyl, and riboflavin, in rats that were exposed to 850 R cobalt-60 gamma-radiation or sham irradiated. In one series of experiments, the drugs were administered orally and the amount of drug excreted in urine was used as a measure of the extent of their absorption. Cumulative urinary excretion of the drugs was shown to be a valid measure of absorption since it was not affected by radiation after intravenous administration of the drugs. At one day post-irradiation, the extent of absorption of sulfanilamide and bretylium was not affected by radiation but the absorption of sulfisoxazole acetyl and riboflavin was increased. At five days post-irradiation, there was no detectable difference between irradiated and control animals in the extent of absorption of the drugs. The fraction of sulfanilamide excreted in the urine as 4N-conjugate was increased at one day post-irradiation. The increased excretion of metabolite appeared to result from metabolism of the drug by gut flora prior to absorption. This study shows that radiation-induced alterations in the absorption of orally administered drugs are due primarily to slowed gastric emptying. In general, slowed gastric emptying causes the rate of drug absorption to decline. The extent of absorption of drugs that are normally well absorbed is not affected by radiation while the extent of absorption of drugs that normally are absorbed poorly may be increased after irradiation of the GI tract