Abstract
The purpose of this study was to quantify the effects of aging on gastrointestinal motility and subepithelial blood flow, two important determinants of the bioavailability of orally administered drugs. Polyethylene glycol 4000 (PEG 4000) was administered by gastric intubation to senescent (age 31 months) and mature (age 16 months) female Fischer 344 rats. The rates of gastric emptying and small intestinal transit were determined from measurements of the distribution of PEG 4000 along the GI tract at various times after its administration. Gastric emptying rates were similar in both groups. However, in the senescent rats, the transit rates of the proximal and distal small intestine were considerably higher and significantly lower, respectively, than the corresponding rates in the mature animals. In another experiment, barbital was administered intraperitoneally to anesthetized animals. After 1 hr a 20 cm segment of jejunum was perfused with a pH 9.5 carbonate buffer, and the blood-to-lumen clearance of barbital was determined. The clearance, which was directly related to intestinal subepithelial blood flow, was 4.52 ± 0.58 and 3.92 ± 0.37 μl/min/cm in senescent and mature rats, respectively. No evidence for a senescence-related alteration in intestinal blood flow was observed.
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