Effect of fluid volume on gastric emptying and intestinal drug absorption. II. dihydrocodeine and thiopental concentration profiles in plasma after oral administration in different fluid volumes to mice.

Publisher Website
Google Scholar
Abstract
Dihydrocodeine was orally administered to mice and the effect of fluid volume on intestinal absorption and acute toxicity was investigated. An increase in fluid volume from 5 to 20 ml/kg resulted in a significant increase in maximum plasma dihydrocodeine concentration (Cmax); the time required to reach Cmax(Tmax) was reduced from 15 to 5 min. Fluid volume had little effect on the area under the plasma dihydrocodeine concentration-time curve (AUC0 .fwdarw. 90). The acute toxicity of dihydrocodeine increased significantly with increasing fluid volume and the gastric emptying rate of dihydrocodeine in the initial stage after oral administration increased in proportion to the fluid volume. These results indicate that early acceleration of the gastric emptying rate due to the increase of fluid volume increases the rate but not the extent of dihydrocodeine absorption, resulting in the enhancement of acute toxicity. As for thiopental, the influence of volume on intestinal absorption was examined by using [35S]thiopental. The Cmax value increased and Tmax was reduced from 20 to 5 min by increase of the fluid volume. The volume did not influence AUC0 .fwdarw. 90 values.