Short-term effects of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor on cholesterol and bile acid synthesis in humans.
Competitive inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase improve hypercholesterolemia. However, reports about the effects of these agents on bile acid synthesis, the metabolic pathway of cholesterol, are conflicting. We studied the short-term effect on one of these agents, pravastatin, on bile acid synthesis. Six male volunteers were given 40 mg of pravastatin. Plasma mevalonate level (which reflects cholesterol synthesis) and 7 alpha-hydroxy-4-cholesten-3-one level (which reflects bile acid synthesis) were measured every 2 h for 8 h. These plasma levels were compared to those of the same volunteers without pravastatin. Plasma mevalonate level after 2 h was lower than control (3.0 +/- 1.1 ng/mL vs. 6.7 +/- 2.5, mean +/- SD; P < 0.05). This decrease continued for 8 h (2.5 +/- 0.8 vs. 5.2 +/- 1.5; P < 0.05). On the other hand, plasma 7 alpha-hydroxy-4-cholesten-3-one level did not change until after 6 h; then at 8 h it was lower than control (15.7 +/- 11.8 ng/mL vs. 24.7 +/- 16.9; P < 0.05). According to three-way layout analysis of variance, mevalonate level was influenced by both pravastatin treatment (P < 0.01) and time-course (P < 0.01). On the other hand, the 7 alpha-hydroxy-4-cholesten-3-one level was affected by both individual difference (P < 0.01) and time course (P < 0.01), but pravastatin treatment did not influence this compound. This indicates that bile acid synthesis was influenced by pravastatin, although cholesterol synthesis was inhibited. The short-term inhibition of cholesterol synthesis did not affect bile acid synthesis.
Yoshida
T
T
Department of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Honda
A
A
Shoda
J
J
Abei
M
M
Matsuzaki
Y
Y
Tanaka
N
N
Miyazaki
H
H
Osuga
T
T
D000328:Adult; D000704:Analysis of Variance; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002783:Cholestenones / Q000097:blood; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D002940:Circadian Rhythm; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008798:Mevalonic Acid / Q000097:blood; D017035:Pravastatin / Q000097:blood / Q000494:pharmacology*
D001647:Bile Acids and Salts; D002783:Cholestenones; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008079:Lipoproteins, VLDL; D002784:Cholesterol; D017035:Pravastatin; D008798:Mevalonic Acid