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(Circulation. 1972;46:95.)
© 1972 American Heart Association, Inc.

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Mechanisms of Action of Cholestyramine in the Treatment of Hypercholesterolemia

D. J. NAZIR PH.D.¹; L. HORLICK M.D.¹; B. J. KUDCHODKAR PH.D.¹; H. S. SODHI M.D., PH.D.¹

¹ From the Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

Cholestyramine (12 g/day) was administered to four subjects with familial hyperchloesterolemia (type II) for 12 to 15 days. Plasma cholesterol values fell by 24 to 28% in all subjects. Total endogenous fecal steroids increased from 2.0 to 2.5 times over the control values. This increment was mainly in the acidic fraction which increased from 1.4 to 6.5 times during treatment. The neutral steroid fraction showed a slight increase (nonsignificant) in two subjects and a significant increase (P < 0.05) in one subject. The total fecal steroid increment was considerably in excess of the decrement in plasma cholesterol, thus indicating either (a) a substantial increase in cholesterol synthesis, (b) a transfer of cholesterol from depots, or (c) both. Plasma cholesterol specific activity time curves showed a sharp increase in the slope immediately after the commencement of treatment, reflecting an increase in the rate of entry of unlabeled cholesterol into the readily miscible pool. Since cholestyramine did not change the absorption of the dietary cholesterol, the increase in the contribution of unlabeled cholesterol could only be from an increase in endogenous synthesis. In accordance with previous findings from this laboratory, no evidence of degradation of the steroid nucleus was detected during its passage through the gastrointestinal tract.

Key Words: Plasma cholesterol • Cholesterol absorption • Cholesterol synthesis • Cholesterol degradation • Fecal neutral steroids • Fecal bile acids

Submitted on November 23, 1971
Accepted on February 9, 1972

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