ABSORPTION BEHAVIOR OF ORALLY-ADMINISTERED DRUGS IN RATS TREATED WITHPROPANTHELINE

The effect of gastrointestinal (GI) transit rate on the absorption beh avior of orally administered drugs was investigated using rats pretrea ted with propantheline. The propantheline-treatment reduced the transi t rate in all segments to approximately 50%. The absorption behavior w as examined for three model drugs with different absorption characteri stics: theophylline as a highly absorbable drug without the first-pass elimination, ampicillin as a poorly absorbable one, and cephalexin as a highly absorbable one via carrier-mediated transport system. In the GI transit-retarded state, the T-max of the plasma concentration-time curve was delayed in all the three drugs. However, the extent of bioa vailability was not changed in theophylline and cephalexin. On the oth er hand, the extent of bioavailability of ampicillin was increased in rats pretreated with propantheline. This might be caused by the increa sed residence time in the absorption site, i.e., small intestine. Thes e results were generally predicted by use of the convolution method ba sed on the GI-Transit-Absorption Model, which was developed in our pre vious study, using the GI transit rate parameters in rats pretreated w ith propantheline. The analysis using this model could clarify that th e substantial absorption site of cephalexin moved to the upper region of the small intestine by the reduction of the GI transit rate.