Evaluation of the fractional absorption of D-xylose by analysis of gastrointestinal disposition after oral administration in rats.
As an efficient method for estimating the amount orally absorbed, the fraction of D-xylose absorbed in rats was estimated from the ratio of the fecally excreted proportion of D-xylose dose to that of polyethylene glycol (PEG) 4000 as a nonabsorbable marker (D-xylose/PEG 4000 ratio). The D-xylose/PEG 4000 ratio was demonstrated to be independent of the fecal excretion of D-xylose and PEG 4000 (or sampling period), suggesting that it can represent the fraction of the total dose remaining. This result was consistent with the theoretical prediction based on the assumptions that every small fraction of dose behaves in the same manner with regard to absorption and transit through the absorption site (small intestine), and that the gastrointestinal transit of PEG 4000 is identical with that of D-xylose. The fraction of D-xylose absorbed was estimated to be 95.9% by subtracting the remaining fraction (D-xylose/PEG 4000 ratio) from unity (100%). The D-xylose/PEG 4000 ratio, or drug/marker ratio in general, can be determined before fecal excretion is completed. Thus it can provide an efficient way for estimating the fraction of a drug absorbed that is stable in the gastrointestinal tract, such as D-xylose. Although this proposed method of estimating a fraction is generally not applicable unless a given drug is proved to be stable in the gastrointestinal tract, it can be an efficient screening method to identify poorly absorbable drugs. It is especially useful in basic studies and preclinical tests in laboratory animals.
Yuasa
H
H
Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Kuno
C
C
Watanabe
J
J
D000284:Administration, Oral; D000818:Animals; D004064:Digestive System / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D005772:Gastrointestinal Transit; D007408:Intestinal Absorption; D008297:Male; D008954:Models, Biological; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014994:Xylose / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*
D011092:Polyethylene Glycols; D014994:Xylose