Amelioration of methotrexate-induced malabsorption by vitamin A.
Methotrexate (MTX) induces damage to the small intestine, resulting in malabsorption and diarrhea. We found that the coadministration of vitamin A (VA) with MTX protected the small intestine from MTX-induced damage. In this study, the permeability of D-glucose, D-xylose and L-leucine through the small intestine of rats treated with MTX and/or VA was studied using everted segments of small intestine. MTX treatment decreased permeability and VA coadministration prevented the decrease. The transport of D-glucose in the small intestine of MTX plus VA- and VA-treated rats and of control rats followed Michaelis-Menten kinetics, in contrast to the transport kinetics in MTX-treated rats. The pharmacokinetics of orally administered [14C]-D-glucose in control rats and MTX- and/or VA-treated rats was also studied. The bioavailability of D-glucose in MTX-treated rats was lower than in the other three groups. VA coadministration improved the bioavailability of D-glucose. Thus, it seems likely that VA ameliorates MTX-induced malabsorption.
Yamamoto
J
J
Department of Biopharmaceutics, Tokyo University of Pharmacy and Life Science, Japan.
Horie
T
T
Awazu
S
S
D000284:Administration, Oral; D000596:Amino Acids / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D005947:Glucose / Q000008:administration & dosage / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D008286:Malabsorption Syndromes / Q000139:chemically induced / Q000517:prevention & control*; D008727:Methotrexate / Q000009:adverse effects*; D051381:Rats; D014801:Vitamin A / Q000494:pharmacology*
D000596:Amino Acids; D000964:Antimetabolites, Antineoplastic; D014801:Vitamin A; D005947:Glucose; D008727:Methotrexate