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 imp rove 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 agen ts, pravastatin, on bile acid synthesis. Six male volunteers were give n 40 mg of pravastatin. Plasma mevalonate level (which reflects choles terol synthesis) and 7 alpha-hydroxy-4-cholesten-3-one level (which re flects bile acid synthesis) were measured every 2 h for 8 h. These pla sma levels were compared to those of the same volunteers without prava statin. 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 c ontinued 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 u ntil after 6 h; then at 8 h it was lower than control (15.7 +/- 11.8 n g/mL vs. 24.7 +/- 16.9; P < 0.05). According to three-way layout analy sis of variance, mevalonate level was influenced by both pravastatin t reatment (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 individu al difference (P < 0.01) and time course (P < 0.01), but pravastatin t reatment did not influence this compound. This indicates that bile aci d synthesis was not influenced by pravastatin, although cholesterol sy nthesis was inhibited. The shortterm inhibition of cholesterol synthes is did not affect bile acid synthesis.