Mode of action of a new hypocholesteraemic drug (DH-581) in familial hypercholesteraemia

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      DH-581, a new hypocholesteraemic agent, reduced serum free and esterified cholesterol by 27% in 5 patients with familial hypercholesteraemia during a treatment period of 4 weeks. Triglycerides slightly increased in the serum and decreased in the liver, while hepatic cholesterol was unchanged. Faecal bile acids, fat and water were increased especially during the transitional period when serum cholesterol was decreasing. At that time cholesterol absorption and serum methyl sterols (used as an index of cholesterol synthesis) were decreased, the increment of faecal elimination of cholesterol from endogenous sources remaining insignificant. However, faecal steroid values were significantly lower at the end of treatment than during the transitional period, neutral steroids of endogenous origin being even lower than initially. No adverse side effects were recorded. The plasma insulin response to glucose was increased on the drug, while the thyroxine-binding capacity and the plasma activity of heparin-induced lipoprotein lipase were reduced.


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      1. Mollelo, J. A., Dow Chemical Co., Zionsville, Ind., Personal communication.

      2. Colmore, J. P., Dow Chemical Co, Zionsville, Ind., Personal communication.

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