Abstract
Purpose. By varying stool water content using lactulose and codeine, we investigated the influence of luminal water content on the absorption of quinine, a transcellular probe, and 5lCr-EDTA, a paracellular probe, from the distal gut.
Methods. Sixteen volunteers entered a three-way cross-over trial in which absorption of probe markers from a timed-release delivery system was determined following treatment with lactulose 20 mls tds (increasing water content), or codeine 30 gms qds (decreasing water content), and compared with control untreated values. Stool water content was assessed by freeze drying stool samples. Site of release was determined by gamma scintigraphy, and absorption was measured by plasma levels and urinary recovery of the marker probes.
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 score 3.4 ± 0.3 vs 1.8 ± 0.2, p < 0.01), and enhanced absorption of the transcellular probe quinine (4.66 ± 0.78 vs 3.02 ± 0.63%, p < 0.05) compared 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 tended to diminish absorption (2.60 ± 0.77 vs 3.02 ± 0.63%, p = 0.20). Within the ascending colon specifically, there was a significant trend for treatments increasing luminal water content to enhance quinine absorption (medians: 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 absorption, with more distal release resulting in less absorption in the control 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 transit, decreases stool water content, and tends to diminish absorption, compared to controls. We conclude that water content may be an important determinant in colonic drug absorption.
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REFERENCES
A. H. Staib, D. Beermann, S. Harder, U. Fuhr, and D. Liermann. Absorption differences of ciprofloxacin along the human gastrointestinal tract determined using a remote-control drug delivery device (HF-capsule). Am. J. Med. 87:66S-69S (1989).
J. M. Hebden, A. C. Perkins, P. J. Gilchrist, P. E. Blackshaw, C. G. Wilson, and R. C. Spiller. A dual radionuclide study for the investigation of colonic drug delivery and absorption. Nucl. Med. Commun. 16:232 (1995).
G. R. Davis, C. A. Santa Ana, S. G. Morawski, and J. S. Fordtran. Permeability characteristics of human jejunum, ileum, proximal colon and distal colon: results of potential difference measurements and unidirectional fluxes. Gastroenterology 83:844-50 (1982).
R. Levitan, J. S. Fordtran, B. A. Burrows, and F. J. Ingelfinger. Water and salt absorption in the human colon. J. Clin. Invest. 41:1754-59 (1962).
B. Krevsky, L. S. Malmud, F. D'Ercole, A. H. Maurer, and R. S. Fisher. Colonic transit scintigraphy: a physiological approach to the quantitative measurement of colonic transit in humans. Gastroenterology 91:1102-12 (1986).
A. R. Zoest, S. Wanwimolruk, and C. T. Hung. Simple highperformance liquid chromatographic method for the analysis of quinine in human plasma without extraction. J. Liquid Chromatogr. 13:3481-91 (1990).
J. C. Debongnie and S. F. Phillips. Capacity of the human colon to absorb fluid. Gastroenterology 74:698-703 (1978).
R. D. Pullan, G. A. O. Thomas, M. Rhodes, R. G. Newcombe, G. T. Williams, A. Allen, and J. Rhodes. Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis. Gut 35:353-59 (1994).
L. Barrow, K. P. Steed, R. C. Spiller, P. J. Watts, C. D. Melia, M. C. Davies, and C. G. Wilson. Scintigraphic demonstration of lactulose-induced accelerated proximal colon transit. Gastroenterology 103:1167-73 (1992).
I. Bjarnason, C. O'Morain, A. J. Levi, and T. J. Peters. Absorption of 51Chromium-labeled ethylenediaminetetraacetate in inflammatory bowel disease. Gastroenterology 85:318-22 (1983).
D. G. Maxton, I. Bjarnason, A. P. Reynolds, S. D. Catt, T. J. Peters, and I. S. Menzies. Lactulose, 51Cr-labelled ethylenediaminetetra-acetate, L-rhamnose and polyethyleneglycol 500 as probe markers for asessment in vivo of human intestinal permeability. Clin. Sci. 71:71-80 (1986).
M. Elia, R. Behrens, C. Northrop, P. Wraight, and G. Neale. Evaluation of mannitol, lactulose, and 51Cr-labelled ethylenediaminetetra-acetate as markers of intestinal permeability in man. Clin. Sci. 73:197-204 (1987).
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Hebden, J.M., Gilchrist, P.J., Perkins, A.C. et al. Stool Water Content and Colonic Drug Absorption: Contrasting Effects of Lactulose and Codeine. Pharm Res 16, 1254–1259 (1999). https://doi.org/10.1023/A:1014805815499
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DOI: https://doi.org/10.1023/A:1014805815499