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Inhibition of cholesterol absorption with CP‐148,623 lowers serum cholesterol in humans
Author(s) -
Harris William S.,
Windsor Sheryl L.,
Newton Fran A.,
Gelfand Robert A.
Publication year - 1997
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(97)90171-5
Subject(s) - medicine , placebo , cholesterol , excretion , endocrinology , hyperlipidemia , feces , sterol , blood lipids , chemistry , biology , diabetes mellitus , paleontology , alternative medicine , pathology
Objective To determine the effects of the reduction of intestinal cholesterol absorption with CP‐148,623 on serum cholesterol levels in men with mild hyperlipidemia. Methods In an outpatient study in a university medical center, healthy male volunteers ( n = 25) with borderline‐high serum cholesterol levels participated in a double‐blind, placebo‐controlled parallel‐group study. A 3‐week dietary run‐in period was followed by 2 weeks of treatment with either CP‐148,623 (300 mg twice a day; n = 12) or placebo ( n = 13). Results Fractional cholesterol absorption (by the dual‐isotope, continuous‐feeding technique), fecal neutral sterol excretion, and serum lipids were measured after the diet run‐in and after the treatment periods. CP‐148,623 caused a marked inhibition (by 38%) of fractional cholesterol absorption (50% ± 2% [baseline] to 31% ± 1%) and a 71% increase in fecal neutral sterol excretion (481 ± 39 mg/day [baseline] to 804 ± 55 mg/day), compared with negligible changes in the placebo group ( p < 0.0001 for both). Mean percent reductions from baseline in serum low‐density lipoprotein (LDL) cholesterol levels were 11.6% with CP‐148,623 (119 ± 17 mg/dl to 104 ± 13 mg/dl) versus a nonsignificant 1.8% reduction with placebo (change with CP‐148,623 versus placebo, p < 0.0002). Conclusions In healthy male volunteers with mild hypercholesterolemia, treatment for 2 weeks with 600 mg/day CP‐148,623 inhibited fractional cholesterol absorption by 35% to 40%, increased fecal neutral sterol excretion by 60% to 70%, and reduced serum LDL cholesterol by 10% to 12%. Clinical Pharmacology & Therapeutics (1997) 61 , 385–389; doi: