The mode of action of the hypocholesteremic
drug neomycin (2 g/day) was studied in four patients. All showed a significant reduction in plasma
cholesterol concentrations (mean 25 percent, range 18-31 percent), and in one of three patients with hyperglyceridemia there was a decrease of plasma
triglycerides of 26 percent.
Cholesterol absorption was measured in three of four patients: there was a marked decrease.
Sterol balance studies in four patients showed an unabating increase in fecal neutral
steroid excretion (mean increase 345 mg/day, range 323-361) for 3-5 wk after plasma
cholesterol levels had reached a new and lower plateau. Fecal acidic
steroid excretion increased temporarily in two patients, with a sustained increase of 93 mg/day in only one. Daily stool weights increased significantly in three of four patients, though none had
steatorrhea; there was a significant reduction in excretion of secondary
bile acids; neutral
sterol degradation rates were not affected by the
drug. Slopes of plasma
cholesterol-specific activity time curves did not change. These results fail to support the suggestion that
neomycin acts as a
bile acid precipitant. The finding of increased fecal neutral
steroid excretion is consistent with decreased
cholesterol absorption, but also with increased
cholesterol absorption, but also with increased
cholesterol synthesis (secondary to release of negative feedback control), with increased flux of
cholesterol from tissues, or with a combination of all three actions.