Intestinal active absorption of sugar-conjugated compounds by glucose transport system: implication of improvement of poorly absorbable drugs.
The intestinal absorption of glucose- and galactose-conjugated compounds was studied in the everted sac of the rat small intestine. The absorption clearance of p-nitrophenyl beta-D-glucopyranoside (p-NPglc) at 250 microM in the mucosal side (4.45 +/- 0.34 microL/min/cm, mean +/- SE, N = 4), calculated by dividing the absorption rate by the drug concentration, was significantly decreased (0.476 +/- 0.036 microL/min/cm) in the presence of 1 mM phloridzin, an inhibitor of glucose transport, and in the absence of Na+, a cosubstrate of the glucose transport carrier (0.424 +/- 0.018 microL/min/cm). The absorption clearance of p-NPglc was decreased as its concentration increased. In the same experiment, the absorption clearance of p-nitrophenyl beta-D-galactopyranoside (1.99 +/- 0.23 microL/min/cm) was also significantly decreased in the presence of phloridzin and in the absence of Na+. However, the absorption clearance of p-nitrophenyl beta-D-mannopyranoside (0.811 +/- 0.013 microL/min/cm) was low and not significantly decreased in the presence of phloridzin (P greater than 0.1). Furthermore, the absorption clearance of beta-naphthyl beta-D-glucopyranoside and beta-naphthyl beta-D-galactopyranoside was also significantly decreased in the presence of phloridzin (P less than 0.001). These results indicated that the glucose and galactose moieties provided these compounds with a new route by way of the glucose transport carrier for intestinal absorption.
Mizuma
T
T
Department of Biopharmaceutics, Tokyo College of Pharmacy, Japan.
Ohta
K
K
Hayashi
M
M
Awazu
S
S
D000818:Animals; D001692:Biological Transport; D004337:Drug Carriers; D005690:Galactose / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005960:Glucosides / Q000378:metabolism; D007408:Intestinal Absorption; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009284:Naphthols / Q000378:metabolism; D010695:Phlorhizin / Q000494:pharmacology; D051381:Rats
D004337:Drug Carriers; D005960:Glucosides; D009004:Monosaccharide Transport Proteins; D009284:Naphthols; C025193:4-nitrophenyl beta-D-glucoside; D010695:Phlorhizin; D005947:Glucose; C028405:2-naphthol; D005690:Galactose