Effects of ageing on the oral absorption of D-xylose in rats: analysis of gastrointestinal disposition.
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.
Yuasa
H
H
Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Kawanishi
K
K
Watanabe
J
J
D000284:Administration, Oral; D000375:Aging / Q000378:metabolism*; D000818:Animals; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005753:Gastric Mucosa / Q000378:metabolism; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D007444:Inulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D013270:Stomach / Q000187:drug effects; D014994:Xylose / Q000008:administration & dosage / Q000493:pharmacokinetics*
D007444:Inulin; D014994:Xylose