INCREASED GASTROINTESTINAL ABSORPTION OF LARGE MOLECULES IN PATIENTS AFTER 5-FLUOROURACIL THERAPY FOR METASTATIC COLON-CARCINOMA

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (10) , 3430-3436
Abstract
Chemotherapeutic agents may damage gastrointestinal epithelium and impair the mucosal barrier to bacteria and their products. To obtain an objective measurement of gastrointestinal permeability to large molecules, urinary excretion of [14C]polyvinylpyrrolidone administered orally (mean MW 11,000) and tobramycin (MW 467) was measured in 10 patients receiving 5-fluorouracil therapy for metastatic cancer of the colon. Base-line absorption of [14C]polyvinylpyrrolidone was 0.013 to 0.048% of the administered dose. Dose-related increases in absorption (range, 2- to 20-fold) occurred after 5-fluorouracil administration; the dose response differed markedly between individuals. Absorption was maximal 8 to 15 days after the start of therapy, was correlated in time but not necessarily in severity with the presence of gastrointestinal symptoms and was unaffected by oral nonabsorbable antibiotics. Tobramycin excretion was 8.5 times greater than [14C]polyvinylpyrrolidone excretion; the 2 were highly correlated in simultaneous determinations (r = 0.93; P < 0.001). With the exception of an episode of Escherichia coli bacteremia, infections coincided not with maximal [14C]polyvinylpyrrolidone absorption but with maximal granulocytopenia 17 to 24 days after the start of therapy. The gastrointestinal absorption of polyvinylpyrrolidone provides an objective measurement of mucosal integrity which may have applications in assessing the gastrointestinal toxicity of other cytotoxic agents.

This publication has 3 references indexed in Scilit: