To clarify the pharmacological mechanism of
ezetimibe,
SCH 58053, an analog of
ezetimibe, was intraduodenally administered to lymph-
fistula rats, and its effect on lymphatic
lipid transport in the intestine was monitored.
SCH 58053, 5.0 mg/kg
body weight, was administered one hour before a 5-hour infusion of a
lipid emulsion containing 40 micromol/h of
triolein and 2.74 micromol/h of
cholesterol (Experiment 1) or co-administered at 5.0 mg/kg
body weight/h with the
lipid emulsion for 4 hours to rats that had been infused with the
lipid emulsion alone for 3 hours (Experiment 2).
SCH 58053 administration significantly inhibited lymphatic
cholesterol transport, but not
triglyceride transport, in both groups compared to control rats that did not receive
SCH 58053. The ratio of free
cholesterol to total
cholesterol in the lymph of the treated rats was unchanged compared to the control rats. Thus, the results showed that
SCH 58053 is a potent, rapid, and selective inhibitor of lymphatic
cholesterol transport in the intestine.