Stool water content and colonic drug absorption: contrasting effects of lactulose and codeine.
OBJECTIVE
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 51Cr-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 = 81 < control = 2.3%, [n = 5] < lactulose = 3.2%, [n = 71, 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.
Hebden
J M
JM
Division of Gastroenterology, University Hospital Nottingham, UK.
Gilchrist
P J
PJ
Perkins
A C
AC
Wilson
C G
CG
Spiller
R C
RC
D000328:Adult; D001834:Body Water / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003061:Codeine / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D018592:Cross-Over Studies; D004058:Diffusion; D016503:Drug Delivery Systems; D004492:Edetic Acid / Q000493:pharmacokinetics; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007792:Lactulose / Q000494:pharmacology*; D008297:Male; D011803:Quinine / Q000493:pharmacokinetics; D012117:Resins, Synthetic / Q000737:chemistry
D012117:Resins, Synthetic; D007792:Lactulose; C046797:amberlite; D004492:Edetic Acid; D011803:Quinine; D003061:Codeine