Metformin is eliminated by the kidneys, and metformin accumulation has alwa
ys been noticed in oligo-anuric patients. We have reported an exception to
the rule with the case of a metformin-treated patient having metformin accu
mulation contrasting with a mild increase in serum creatinine in the contex
t of a volvulus of the sigmoid colon. This case prompted us to examine the
association between intestinal occlusion and plasma metformin concentration
s. For this purpose, we developed an experimental animal model of mechanica
l obstruction of the intestine. Rats were pre-treated during 3 weeks via dr
inking solution at a dose of approximate to 100 mg/kg/day of metformin. The
y underwent at day 0 either sham-operation (n = 7) or operation (n = 8) to
place a plastic tube around the ileum near the ileocaecal valve. Metformin
administration was pursued on days 1, 2, and 3 giving a single dose of 100
mg/kg by intragastric gavage. Four days after the surgery, i.e. 24 h after
the last metformin administration, the surviving intestinal obstructed rats
(n = 8) developed overt intestinal dilation but no biochemical abnormality
compared to sham-operated animals in 7; arterial lactate concentrations re
spectively 4.87 +/- 0.63 mmol/l and 3.97 +/- 0.30 mmol/l, NS, and serum cre
atinine concentrations 69.0 +/- 1.7 mu mol/l and 68.7 +/- 1.9 mu mol/l, NS)
. By contrast, there was a striking difference with regard to metformin con
centrations, decreasing from 2.95 +/- 0.94 mg/l at day 0 to 0.12 +/- 0.03 m
g/l at day 4 (p < 0.001) in the sham-operated group hut remaining unchanged
(1.65 +/- 0.76 mg/l and 1.61 +/- 0.51 mg/l) in the operation group. In con
clusion, this is the first experiment showing that intestinal occlusion may
be responsible for metformin retention in the absence of renal failure. Wh
ether this observation may be relevant to other drugs remains to be establi
shed.