Turnover of low density lipoproteins during inhibition of cholesterol absorption by neomycin.

The mechanisms for the hypocholesterolemic actin of neomycin were examined in six patients with various levels of plasma total cholesterol and triglycerides. All patients were studied on a metabolic ward. The first period of 6 weeks was for control. Thereafter, neomycin (1.5 g/day) was started, and the patients were readmitted for another 6-week period after 2 to 3 months of treatment with the drug. Cholesterol balance studies showed that neomycin increased fecal excretion of neutral steroids by an average of 45%; the drug also inhibited absorption of exogenous cholesterol by an average of 44%. During treatment with neomycin, the plasma total cholesterol fell by an average of 20%, low density lipoproteins (LDL) fell by 25%, and high density lipoproteins, by 16%. Neomycin did not change plasma triglyceride levels. Turnover of the apoprotein of LDL (apoLDL) was measured following injection of 125I-apoLDL. Neomycin decreased synthesis of apoLDL by 28%. The decrease in plasma apoLDL level was correlated positively with the decrease in apoLDL synthetic rate. The effect of the drug on clearance of LDL was less constant; four of six patients had an increase in fractional clearance rates of apoLDL, but the change for the whole group was not statistically significant. These data suggest that a decrease in production of LDL is a major factor in the lowering of LDL following inhibition of cholesterol absorption; however, an increase in clearance rates may occur in some patients.