Effects of Ageing on the Oral Absorption of d-Xylose in Rats: Analysis of Gastrointestinal Disposition

Abstract

The effects of ageing on the oral (gastrointestinal) absorption of D-xylose were investigated by analysing the gastrointestinal disposition after oral administration to young (9 weeks) and old (53 weeks) rats. A linear model assuming first-order gastric emptying followed by first-order intestinal absorption was fitted to remaining fraction vs time profiles for the stomach and small intestine to estimate the gastric emptying rate constant (kg) and the intestinal absorption rate constant (ka). In young and old rats, Kg values were 0.087 +/- 0.008 and 0.070 +/- 0.007 min-1, respectively, and ka values were 0.020 +/- 0.002 and 0.018 +/- 0.002 min-1, suggesting an insignificant effect on ageing on the rate of oral absorption. The average intestinal lumen volume (Vav) was unchanged with ageing, and so was the apparent intestinal membrane permeability clearance (CLapp) as the product of Ka and Vav. However, the small intestinal transit time (Tsi) was suggested to be twice that in older rats (171 min) than in young rats (78 min) by the analysis of gastrointestinal disposition of inulin, a non-absorbable marker. It was also shown that our preceding finding of an increase in the fraction absorbed of D-xylose with ageing can be solely ascribable to the delay in intestinal transit. Thus, among various determinants of oral absorption, only Tsi was found to be altered with ageing. The CLa,app and ka of passively absorbed drugs such as D-xylose may be generally unchanged, and the fraction absorbed may increase with ageing by the delay in intestinal transit.

Ileal bile acid transporter inhibition, CYP7A1 induction, and antilipemic action of 264W94

“…Compared with the in situ model where effects occurred within 4 min, the time of onset of inhibition of IBAT in rats, having bile acid pools equilibrated with 75 SeHCAT, was delayed by 1 h to 2 h when 264W94 was administered orally. The time of onset is most likely dependent on intestinal transit time for the active compound to reach the distal ileum, and is consistent with the physiological small intestinal transit time of 78 min reported for normal rats of comparable age (33). In the distal quarter of the small intestine, peak inhibition of bile acid absorption of 97% and 52% at 4 h and 6 h, respectively, after oral dosing with 264W94, was synchronous with the appearance of increased 75 SeHCAT content (159% and 84%, respectively) in the large intestine, and consistent with the 232% increase in fecal 75 SeHCAT excretion with a comparable dose in a 24 h period.…”

“…For kinetic studies, initial uptake velocities were determined in a 10-min incubation period. Kinetic parameters were determined by using a 4 ϫ 5 matrix of inhibitor (0, 0.1, 0.2, and 0.3 M 264W94) and substrate (11,14,20,33, and 100 M [ 3 H]TC) concentrations, under the general assay conditions described above. Initial uptake velocities are expressed in picomoles per milligram of cell protein per minute.…”

Influence of aging on experimental gastrointestinal motility in extraction of rat molar teeth

“…Furthermore, No differences were observed in the gastric emptying rates between young and senior cats 25) . This corroborates results from studies in both humans 26) and rats 27) where ageing was reported to have no effect on the rate of gastric emptying.…”

“…One effect of ageing is a decrease in apparent nutrient digestibility in the gastrointestinal tract 12) . This has been observed in many species including humans 13) , rats 14) . Age variation is a further complication that must be addressed, since the relative of chewing and gastrointestinal tract is still unclear.…”

Physiological mechanism-based analysis of dose-dependent gastrointestinal absorption ofl-carnitine in rats

“…, respectively, and small intestinal transit time (T si ) of 78 min from our previous study [21], assuming that F a,oral is, at each dose, defined by linear absorption in the small intestine (F a,oral = 1− e − k a · T si ) [21,22]. Thus, it is suggested that the dose-dependence of F can be quantitatively accounted for by that of F a,oral due to the saturable intestinal transport.…”