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

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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 (C_<max>); the time required to reach C_<max> (T_<max>) was reduced from 15 to 5 min. However, fluid volume had little effect on the area under the plasma dihydrocodeine concentration-time curve (AUC_<0→90>). The acute toxicity 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 fluid volume on intestinal absorption was also examined using [^<35>S]-thiopental. The C_<max> value increased and T_<max> was reduced from 20 to 5 min by increase of the fluid volume. However, the volume did not influence AUC_<0→60> values.
公益社団法人日本薬学会の論文
1982-05-25