Yamamoto J, Horie T, Awazu S
Department of Biopharmaceutics, Tokyo University of Pharmacy and Life Science, Japan.
Cancer Chemother Pharmacol. 1997;39(3):239-44. doi: 10.1007/s002800050567.
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.
甲氨蝶呤（MTX）会导致小肠损伤，进而引起吸收不良和腹泻。我们发现，维生素A（VA）与MTX联合使用可保护小肠免受MTX诱导的损伤。在本研究中，使用外翻小肠段研究了MTX和/或VA处理的大鼠小肠对D-葡萄糖、D-木糖和L-亮氨酸的通透性。MTX处理降低了通透性，而VA联合给药可防止这种降低。与MTX处理的大鼠相比，MTX加VA和VA处理的大鼠以及对照大鼠小肠中D-葡萄糖的转运遵循米氏动力学。还研究了口服[14C]-D-葡萄糖在对照大鼠以及MTX和/或VA处理的大鼠中的药代动力学。MTX处理的大鼠中D-葡萄糖的生物利用度低于其他三组。VA联合给药提高了D-葡萄糖的生物利用度。因此，VA似乎可以改善MTX诱导的吸收不良。
