Abstract:
: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.
journal_name
Lipidsjournal_title
Lipidsauthors
Yoshida T,Honda A,Shoda J,Abei M,Matsuzaki Y,Tanaka N,Miyazaki H,Osuga Tdoi
10.1007/s11745-997-0112-2subject
Has Abstractpub_date
1997-08-01 00:00:00pages
873-8issue
8eissn
0024-4201issn
1558-9307journal_volume
32pub_type
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