Evaluation of absorption kinetics of orally administered theophylline in rats based on gastrointestinal transit monitoring by gamma scintigraphy

The gastrointestinal (GI) transit and absorption of orally administered the ophylline, a highly absorbable drug without presystemic elimination, were i nvestigated under fasted and fed conditions using three rats in a crossover study. To evaluate the GI transit rate for each segment in vivo, a noninva sive technique, gamma scintigraphy, was employed using a nonabsorbable comp ound, Tc-99m-labeled diethylenetriamine pentaacetic acid (DTPA). Using a ga mma scintigraphic technique it is possible to simultaneously evaluate the G I transit and absorption of orally administered drug in the same individual . Theophylline was simultaneously administered along with [Tc-99m]DTpA to a nimals in the fasted and fed states. Each GI transit pattern, simulated usi ng the GI transit-kinetic model with a lag time factor, was well fitted to the experimental data. Gastric emptying rate varied in each study, even und er the same experimental condition. The GI transit pattern for each segment was highly variable, especially in animals in the fed state. This inconsis tency in transit pattern was mainly due to the variability in gastric empty ing, which was much slower in animals in the fed compared with the fasted s tate. However, in spite of a large variability of GI transit kinetics, the plasma concentration-time curves of theophylline were well predicted by the GI transit-absorption model using the individual GI transit parameters obt ained in the study. The absorption rate of theophylline was considerably re duced in animals in the fed state, because of the reduction of gastric empt ying rate. Analysis using GI transit-absorption model and gamma scintigraph ic technique made it possible to estimate the variable absorption kinetics regulated by GI transit with huge variability. (C) 2001 Wiley-Liss, Inc. an d the American Pharmaceutical Association J Pharm Sci 90:464-473, 2001.