Low-Dose Methotrexate-Induced Changes in Intestinal Permeability Determined by Polyethylene Glycol Polymers

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Abstract
The impact of chemotherapeutic agents on small bowel mucosa has not been investigated adequately in children. To determine the effect of low-dose methotrexate (MTX) on the permeability and mucosal integrity of the small bowel, we administered low molecular weight polyethylene glycol (PEG) to 19 children who were in the maintenance phase of treatment of acute lymphocytic leukemia. PEG was administered before and after the children received their weekly oral or intramuscular doses of MTX. PEG recoveries from a 6-h urine collection were calculated by a mathematical formula to determine the polymer with maximal recovery (PCD0) and the polymer whose recovery was 50% of PCDo (N1/2). Compared with pre-MTX levels, a significant increase was observed in the polymer with maximal recovery (PCDo) in 15/19 children after MTX administration (p < 0.015) which indicated increased transmucosal passage of PEG. A decrease in the PEG parameter (N1/2) was observed in 11/38 studies, and may have indicated diminished enterocyte cell mass. These changes indicate that treatment with MTX results in an increase in intestinal permeability by the paracellular pathway, which may affect the absorption of other molecules.