Abstract
Recently, we have found an increased absorption of theophylline in restraint water-immersion stressed rats. We have futher studied the mechanisms involved pharmacologically. First, this stimulatory effect was inhibited by treatment with sodium bicarbo-nate and was related to the degree of stomach damage induced by water-immersion stress inversely. Metochlopramide or sodium picosulfatestimulated the theophylline absorption similar to that by water-immersion stress. These effects were also inhibited by atropine. It was suggested that the stimulatory effect of theophylline absorption was in part caused by the increase of gastro-intestinal movement. Cimetidine has been reported to inhibit the hepatic metabolic enzyme in liver. Indeed, cimetidine pretreatment increased the absorption of theophylline. Pharmacokinetic data have showed that Ka increased by 3 times and Kel decreased by 1/10 compared with control. Rat blood GOT, GPT, ALP and LDH activities were determined in control and stressed rats groups. Among them, LDH activities increased by 6 folds compared with controlrats. This increased LDH actvities have returned to control level by 24 hours after thewater-immersion stress.
In this study, it has showed that the theophylline absorption was increased dominantly by the pretreatment of water-immersion stress. The mechanisms involved in the stimulatory effect would involve some mechanisms such as increased gastro-intestinal movement or decreased hepatic drug metabolism.
