The effect of oral dose volume on the absorption of a highly and a poorly water soluble drug in the rat

The influence of dose volume on drug absorption following oral administration of a highly and a poorly water soluble drug was examined in male Sprague‐Dawley rats. A constant mass of each 14C‐labeled compound was given via gavage in dose volumes of 1, 5, 10, and 20 mL kg−1. Blood levels, as well as the quantitative excretion of radioactivity, were measured following each treatment. No significant changes in either the rate or extent of absorption of the water soluble drug were detected. In contrast, the absorption rate of the poorly water soluble drug increased with higher dose volumes, whereas no changes in the extent of absorption were observed. Drug solubility and gastric emptying appeared to be important factors affecting the rate of absorption of the poorly water soluble drug. Since changes in dose volume may affect the absorption characteristics of orally administered compounds, and the extent of such changes may be dependent upon the physicochemical properties of the drug, it is apparent that dose volume is an important experimental variable to be considered in studies comparing absorption data.