Lack of effect of cholesterol esterase inhibitor CVT-1 on cholesterol absorption and LDL cholesterol in humans

Two clinical trials were performed to test the hypothesis that CVT-1, a pot ent inhibitor of pancreatic cholesterol esterase, reduces percent cholester ol absorption and LDL cholesterol in humans. Measurements of cholesterol ab sorption were made with deuterated cholesterol tracers given orally and int ravenously and detected in plasma by a new technique using negative ion mas s spectrometry. Study 1 was a randomized, double-blind parallel study of CV T-1 treatment of doses of 0, 300, 1500, and 3000 mg/day in 19 subjects. Per cent cholesterol absorption measured at baseline and again after 2 and 6 we eks showed no treatment effect and LDL cholesterol was unchanged. Study II was a randomized open-label crossover comparison between CVT-1 given as 100 0 mg three times daily for 2 weeks and 187.5 mg hourly 16 hours/day for 2 w eeks. Percent cholesterol absorption and plasma LDL cholesterol were not di fferent between periods. We conclude that cholesterol esterase is not requi red for unesterified cholesterol absorption in human subjects.