Generality in effects of transmucosal fluid movement and glucose on drug absorption from the rat small intestine.

Abstract

The generality in effects of transmucosal fluid movement and glucose on drug absorption from the rat small intestine was investigated using twenty three drugs having different charges in the physiological pH of the intestine of the animal with the in situ recirculating perfusion method. All of the regression lines representing the relation between ratio of the transmucosal fluid movement on the vertical axis and intestinal absorption of respective drugs on the horizontal axis were not perpendicular to the horizontal axis but have some inclinations without exception. These evidences did support the concept that intestinal drug absorption was subtly affected by the transmucosal fluid movement and thus the generality in effect of the movement was apparently demonstrated. Concerning the glucose effect, two regression lines, one was of sodium chloride and another was of glucose in the perfusate, were obtained in all of the drugs. However, these two regression lines were overlapped in the cases of unionized drugs. On the other hand, in the cases of cationic drugs the regression lines of glucose were always shifted significantly to the right hand side of those of sodium chloride and in the cases of anionic drugs the regression lines of glucose were shifted to the left hand side without any exception. These evidences demonstrated that glucose increased the absorption of cationic drugs and decreased that of anionic drugs and, moreover, these findings were supported by investigating blood level of respective drugs in the subjected animal. Thus the generality in the glucose effect was apparently demonstrated. Moreover, the glucose effect was also recognized when two drugs were coexisted simultaneously in the perfusate. The glucose effect in drug absorption might be one of mechanisms of drug interactions which have been observed in clinical medicine.