TY - JOUR
T1 - Lack of effect of cholesterol esterase inhibitor CVT-1 on cholesterol absorption and LDL cholesterol in humans
AU - Bosner, Matthew S.
AU - Wolff, Andrew A.
AU - Ostlund, Richard E.
N1 - Funding Information:
Address for correspondence: Richard E. Ostlund, Jr., M.D., Division of Endocrinology, Diabetes and Metabolism, Washington University School of Medicine, 660 South Euclid Ave. Box 8127, St. Louis, MO 63110, Phone: (314) 362-8286, FAX: (314) 747-4471. E-mail: [email protected] This work was supported by a grant from CV Therapeutics, Inc., an American Heart Association Grant in Aid (MSB), NIH Grant R01 HL 50420 (R.E.O.), and the Washington University Mass Spectrometry Resource (RR-00954).
PY - 1999
Y1 - 1999
N2 - Two clinical trials were performed to test the hypothesis that CVT-1, a potent inhibitor of pancreatic cholesterol esterase, reduces percent cholesterol absorption and LDL cholesterol in humans. Measurements of cholesterol absorption were made with deuterated cholesterol tracers given orally and intravenously and detected in plasma by a new technique using negative ion mass spectrometry. Study 1 was a randomized, double-blind parallel study of CVT-1 treatment at doses of 0, 300, 1500, and 3000 mg/day in 19 subjects. Percent cholesterol absorption measured at baseline and again after 2 and 6 weeks showed no treatment effect and LDL cholesterol was unchanged. Study II was a randomized open-label crossover comparison between CVT-1 given as 1000 mg three times daily for 2 weeks and 187.5 mg hourly 16 hours/day for 2 weeks. Percent cholesterol absorption and plasma LDL cholesterol were not different between periods. We conclude that cholesterol esterase is not required for unesterified cholesterol absorption in human subjects.
AB - Two clinical trials were performed to test the hypothesis that CVT-1, a potent inhibitor of pancreatic cholesterol esterase, reduces percent cholesterol absorption and LDL cholesterol in humans. Measurements of cholesterol absorption were made with deuterated cholesterol tracers given orally and intravenously and detected in plasma by a new technique using negative ion mass spectrometry. Study 1 was a randomized, double-blind parallel study of CVT-1 treatment at doses of 0, 300, 1500, and 3000 mg/day in 19 subjects. Percent cholesterol absorption measured at baseline and again after 2 and 6 weeks showed no treatment effect and LDL cholesterol was unchanged. Study II was a randomized open-label crossover comparison between CVT-1 given as 1000 mg three times daily for 2 weeks and 187.5 mg hourly 16 hours/day for 2 weeks. Percent cholesterol absorption and plasma LDL cholesterol were not different between periods. We conclude that cholesterol esterase is not required for unesterified cholesterol absorption in human subjects.
KW - Cholesterol
KW - Cholesterol absorption
KW - Cholesterol esterase
KW - Clinical trial
KW - Mass spectrometry
UR - https://www.scopus.com/pages/publications/0032881789
U2 - 10.1023/A:1007864208932
DO - 10.1023/A:1007864208932
M3 - Article
C2 - 10547226
AN - SCOPUS:0032881789
SN - 0920-3206
VL - 13
SP - 449
EP - 454
JO - Cardiovascular Drugs and Therapy
JF - Cardiovascular Drugs and Therapy
IS - 5
ER -