Inhibition of cholesterol absorption with CP-148,623 lowers serum cholesterol in humans.
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%.
Harris
W S
WS
Department of Medicine, University of Kansas Medical Center, Kansas City, MO, USA.
Windsor
S L
SL
Newton
F A
FA
Gelfand
R A
RA
D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000097:blood*; D005243:Feces / Q000737:chemistry; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D007408:Intestinal Absorption / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008297:Male; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D008055:Lipids; D012503:Saponins; C099629:pamaqueside