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Short‐term effects of 3‐hydroxy‐3‐methylglutaryl‐CoA reductase inhibitor on cholesterol and bile acid synthesis in humans
Author(s) -
Yoshida Tadashi,
Honda Akira,
Shoda Junichi,
Abei Masato,
Matsuzaki Yasushi,
Tanaka Naomi,
Miyazaki Hiroshi,
Osuga Toshiaki
Publication year - 1997
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-997-0112-2
Subject(s) - lipidology , clinical chemistry , reductase , bile acid , cholesterol , term (time) , hmg coa reductase , chemistry , medicine , cholesterol synthesis , biochemistry , endocrinology , pharmacology , enzyme , physics , quantum mechanics
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 of 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 7α‐hydroxy‐4‐cholesten‐3‐one level 9which 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 7α‐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 7α‐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 not influenced by pravastatin, although cholesterol synthesis was inhibited. The shortterm inhibition of cholesterol synthesis did not affect bile acid synthesis.