Colonic transit influences deoxycholic acid kinetics.
OBJECTIVE
Prolonged large bowel transit, and an increase in the proportion of deoxycholic acid (DCA), have been implicated in the pathogenesis of cholesterol gallstones-including those developing in acromegalics treated with octreotide. However, there are few data on the effects of intestinal transit on bile acid kinetics.


METHODS
We therefore measured the kinetics of DCA and cholic acid (CA) using stable isotopes, serum sampling, and mass spectrometry. The results were related to mouth-to-caecum (MCTT) and large bowel transit times (LBTTs) in 4 groups of 8 individuals: (1) non-acromegalic controls, (2) acromegalics untreated with octreotide, (3) acromegalics on long-term octreotide, and (4) patients with constipation. Paired, before and during octreotide, studies were performed in 5 acromegalics.


RESULTS
In the unpaired and paired studies, octreotide significantly prolonged MCTT and LBTT. In the paired studies, the octreotide-induced prolongation of LBTT caused an increase in the DCA input rate (6.4 +/- 2.8 to 12 +/- 2.6 micromol. kg. d, P < 0.05) and pool size (18 +/- 12 to 40 +/- 13 micromol/kg, P < 0.05), and a decrease in CA pool size (45 +/- 15 to 25 +/- 11 micromol/kg, P < 0.05). Furthermore, during octreotide treatment, the mean conversion of 13C-CA to 13C-DCA (micromoles) was greater (P < 0.05) on study days 3, 4, and 5. There were also positive linear relationships between LBTT and DCA input rate (r = 0.78), pool size (r = 0.82, P < 0.001), and a weak (r = -0.49) negative linear relationship between LBTT and CA pool size (P < 0.01).


CONCLUSIONS
These data support the hypothesis that, by increasing DCA formation and absorption, prolongation of large bowel transit is a pathogenic factor in the formation of octreotide-induced gallstones.
Veysey
M J
MJ
Gastroenterology Unit, Guy's Hospital Campus, London, England, UK.
Thomas
L A
LA
Mallet
A I
AI
Jenkins
P J
PJ
Besser
G M
GM
Murphy
G M
GM
Dowling
R H
RH
D000172:Acromegaly / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001835:Body Weight; D002247:Carbon Isotopes; D019826:Cholic Acid / Q000096:biosynthesis / Q000097:blood / Q000493:pharmacokinetics; D003106:Colon / Q000502:physiology* / Q000503:physiopathology; D003840:Deoxycholic Acid / Q000097:blood / Q000493:pharmacokinetics*; D003903:Deuterium; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use; D019518:Postprandial Period
D002247:Carbon Isotopes; D003840:Deoxycholic Acid; D003903:Deuterium; D019826:Cholic Acid; D015282:Octreotide