Inhibiting cholesterol absorption with CP-88,818 (β-tigogenin cellobioside; tiqueside)

Studies in normal and hyperlipidemic subjects

William Harris, Carlos A. Dujovne, Sheryl L. Windsor, Linda L. Colle Gerrond, Fran A. Newton, Robert A. Gelfand

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

CP-88,818 (β-tigogenin cellobioside; tiqueside) is a synthetic saponin developed to treat hypercholesterolemia by inhibiting the absorption of biliary and dietary cholesterol. Two studies are reported here: one in patients to assess safety and efficacy, and one in normal volunteers to explore the mechanism of action. The former included 15 hypercholesterolemic outpatients [low-density lipoprotein cholesterol (LDL-C) >160 mg/dl] treated with 1, 2, and 3 g of tiqueside daily (b.i.d.) in a crossover design for three 2-week treatment periods, each separated by a 3-week placebo period. The mechanistic study was conducted with 24 healthy male subjects who were randomized in s parallel group design to either placebo (n = 6) or tiqueside (2 or 4 g/day; n = 9 each) once daily for 3 weeks. All subjects in this study were fed a low-fat, low-cholesterol diet [National Cholesterol Education Program (NCEP) Step 1 ]. Focal steroid excretion rates and plasma lipid levels were determined at baseline and after 3 weeks of treatment. Fractional cholesterol absorption was measured before and after treatment by the continuous feeding, dual-isotope method. Tiqueside produced a dose-dependent reduction in plasma LDL cholesterol levels in the hypercholesterolemic patients. In the mechanistic study, it decreased fractional cholesterol absorption rates and increased focal neutral sterol excretion rates, changes associated with trends toward lower LDL cholesterol levels. Other lipoprotein levels were unaffected, as were focal fat and bile acid excretion and fat- soluble vitamin absorption. Thus tiqueside dose-dependently inhibits cholesterol absorption in humans, resulting in a reduction in serum LDL cholesterol levels.

Original languageEnglish (US)
Pages (from-to)55-60
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume30
Issue number1
DOIs
StatePublished - Jul 1997
Externally publishedYes

Fingerprint

LDL Cholesterol
Cholesterol
Healthy Volunteers
Fats
Placebos
Dietary Cholesterol
Fat-Restricted Diet
Saponins
Sterols
Hypercholesterolemia
Bile Acids and Salts
Vitamins
Isotopes
Cross-Over Studies
Lipoproteins
Outpatients
Therapeutics
Steroids
tiqueside
sarsasapogenin

Keywords

  • Cholesterol absorption
  • Fecal sterols
  • Hypercholesterolemia
  • Hypolipidemic drugs
  • Saponins

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Inhibiting cholesterol absorption with CP-88,818 (β-tigogenin cellobioside; tiqueside) : Studies in normal and hyperlipidemic subjects. / Harris, William; Dujovne, Carlos A.; Windsor, Sheryl L.; Colle Gerrond, Linda L.; Newton, Fran A.; Gelfand, Robert A.

In: Journal of Cardiovascular Pharmacology, Vol. 30, No. 1, 07.1997, p. 55-60.

Research output: Contribution to journalArticle

Harris, William ; Dujovne, Carlos A. ; Windsor, Sheryl L. ; Colle Gerrond, Linda L. ; Newton, Fran A. ; Gelfand, Robert A. / Inhibiting cholesterol absorption with CP-88,818 (β-tigogenin cellobioside; tiqueside) : Studies in normal and hyperlipidemic subjects. In: Journal of Cardiovascular Pharmacology. 1997 ; Vol. 30, No. 1. pp. 55-60.
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