Stool water content and colonic drug absorption: Contrasting effects of lactulose and codeine

Purpose. By varying stool water content using lactulose and codeine, we inv estigated the influence of luminal water content on the absorption of quini ne, a transcellular probe, and Cr-51-EDTA, a paracellular probe, from the d istal gut. Methods. Sixteen volunteers entered a three-way cross-over trial in which a bsorption of probe markers from a timed-release delivery system was determi ned following treatment with lactulose 20 mls tds (increasing water content ), or codeine 30 gms qds (decreasing water content), and compared with cont rol untreated values. Stool water content was assessed by freeze drying sto ol samples. Site of release was determined by gamma scintigraphy, and absor ption was measured by plasma levels and urinary recovery of the marker prob es. Results. Lactulose accelerated ascending colon transit (3.7 +/- 0.8 vs 4.5 +/- 1.4 hrs, p < 0.05), increased stool water content (75 +/- 2 vs 71 +/- 2 %, p < 0.01), caused greater dispersion of released material (dispersion sc ore 3.4 +/- 0.3 vs 1.8 +/- 0.2, p < 0.01), and enhanced absorption of the t ranscellular probe quinine (4.66 +/- 0.78 vs 3.02 +/- 0.63%, p < 0.05) comp ared to control. Conversely codeine slowed ascending colon transit (8.9 +/- 1.8 hrs), reduced stool water content (61 +/- 2 vs 71.2%, p < 0.05), and t ended to diminish absorption (2.60 +/- 0.77 vs 3.02 +/- 0.63%, p = 0.20). W ithin the ascending colon specifically, there was a significant trend for t reatments increasing luminal water content to enhance quinine absorption (m edians: codeine = 1.2%, [n = 8] < control = 2.3%, [n = 5] < lactulose = 3.2 %, [n = 7], p < 0.01). Delivery site also had an important influence on abs orption, with more distal release resulting iri less absorption in the cont rol arm (medians: small intestine = 4.4% [n = 5] > ascending colon = 2.3% [ n = 5] > transverse colon = 1.5% [n = 6], p < 0.005). Conclusions. Lactulose accelerates transit, increases stool water content, and enhances drug absorption from the distal gut whilst codeine slows trans it, decreases stool water content, and tends to diminish absorption, compar ed to controls. We conclude that water content may be an important determin ant in colonic drug absorption.