Segmental difference and effect of glucose on drug exsorption across the small intestine of rats.
An exsorption technique which can assess the transport of a drug from blood to the intestinal lumen was used to study the effects of glucose and to determine the presence of segmental differences in drug transport across the rat small intestinal membrane following intravenous drug administration. The drugs used in the study were un-ionized (sulfanilamide) or ionized (metoclopramide and sulfisoxazole) at the physiological pH (6.5) of rat small intestine. An intestinal segment of 20 cm from the ligament of Treitz to the distal part was used as the jejunum and the same length from the ileocecal junction to the proximal part was regarded as the ileal segment. Isotonic NaCl or glucose was used as the intraluminal perfusate. In the case of sulfanilamide, the exsorption rate remained almost constant during the perfusion of NaCl or glucose and no segmental differences in the exsorption rates were observed. For the weakly basic drug (metoclopramide) the exsorption rate in the jejunum was significantly decreased by glucose. Conversely, for the weakly acidic drug (sulfisoxazole), the exsorption rate in the jejunum was increased during glucose perfusion. In contrast to the effects observed in the jejunum, glucose did not have any significant effect on the exsorption rate of drugs studied in the ileum. These observations might be explained by the intraluminal pH in the respective segments and changes in the pH mediated by glucose perfusion.
D000818:Animals; D005947:Glucose / Q000494:pharmacology*; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D008787:Metoclopramide / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D000077145:Sulfanilamide; D013424:Sulfanilamides / Q000378:metabolism; D013444:Sulfisoxazole / Q000378:metabolism; D013997:Time Factors
D004364:Pharmaceutical Preparations; D013424:Sulfanilamides; D000077145:Sulfanilamide; D013444:Sulfisoxazole; D005947:Glucose; D008787:Metoclopramide