Effect of the bile-acid sequestrant colestipol on postprandial serum bile-acid concentration: evaluation by bioluminescent enzymic analysis.
Chronic ingestion of bile-acid sequestrants has been shown to decrease the serum cholesterol concentration and coronary events in hypercholesterolaemic patients. To develop improved sequestrants, a rapid, convenient method for testing the bile-acid binding efficacy of sequestrants is needed. Serum bile-acid concentrations could be used to detect bile-acid binding by an administered sequestrant, since the serum bile-acid concentration is determined largely by the rate of intestinal absorption in healthy individuals. To test this, serum bile-acid concentrations were measured at frequent intervals over 24 h in five otherwise healthy hypercholesterolaemic subjects during the ingestion of three standard meals, with or without the addition of 5 g colestipol granules administered 30 min before each meal. Total serum bile-acid concentration was measured with a previously reported bioluminescent enzymic assay, that uses a 3 alpha-hydroxysteroid dehydrogenase, an oxido-reductase, and a bacterial luciferase co-immobilized on to Sepharose beads. Bile acids in 1 ml of serum were isolated by solid-phase extraction chromatography with reversed-phase C18 cartridges. Colestipol lowered the postprandial elevation of serum bile acids by one half, with a subsequent decrease in the cumulative area under the curve. The data suggest that measurement of serum bile-acid concentrations by bioluminescence is a rapid, simple way to document the efficacy of bile-acid sequestrants.
Rossi
S S
SS
Department of Medicine, UC San Diego, La Jolla 92093.
Wayne
M L
ML
Smith
R B
RB
Wright
C E
CE
Andreadis
N A
NA
Hofmann
A F
AF
D000293:Adolescent; D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D003084:Colestipol / Q000494:pharmacology*; D004435:Eating; D004798:Enzymes; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
D001647:Bile Acids and Salts; D004798:Enzymes; D014280:Triglycerides; D002784:Cholesterol; D003084:Colestipol