Effect of 4-(4-Chlorobenzyloxy)benzyl Nicotinate (KCD-232) on Cholesterol Metabolism in Rats Fed an Amino Acid Imbalance Diet

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The effect of KCD-232, a new hypolipidemic agent with the structure of 4-(4-chloro-<benzyloxy)benzyl nicotinate, on cholesterol (Ch) metabolism was studied in rats fed a methioninesupplemented low casein (with threonine imbalance) diet. A methionine-supplemented 10%casein (imbalance) diet caused an increase in serum Ch when compared to a 10%casein diet, while the supplement ofmethionine to a 20%casein diet caused no further increase. In rats fed the imbalance diet, KCD-232reduced the serum Ch level. Measurement of Chabsorption using a dual-isotope serum ratio methodshowedneither an enhancementin the imbalance diet-fed rats nor a reduction in the drug-treated, imbalance diet-fed rats. However, radioactivities in the serum of orally given [3H]Ch and intravenously given [14C]Ch increased in the imbalance diet-fed rats and decreased in the KCD-232-treated rats. Hepatic sterol synthesis measured in vivo using [3H] water was unchanged in the imbalance diet-fed rats and increased in the drug-treated rats. These results suggest that the clearance of Ch from the circulation system, which maybe impaired in rats fed the imbalance diet, is enhanced in the KCD-232-treated, imbalance diet-fed rats.