Effects of lovastatin in humans on biliary lipid composition and secretion as a function of dosage and treatment interval.

Biliary lipid composition and secretion were assessed in nine human subjects in four randomly ordered 3- to 4-week treatment periods during which they took 0 (base line), 20, 40 and 80 mg/day of lovastatin. The mean secretion of cholesterol was lower than base line for each of the three doses but the change reached statistical significance only for the 40- and 80-mg/day doses (P = .004 and .001, respectively). The mean secretion of bile acid and phospholipid was unchanged by any dose of lovastatin. The cholesterol saturation index and molar percent cholesterol in gallbladder bile were both significantly reduced by all doses of lovastatin (P = .001 to .008). For both cholesterol secretion and saturation index, increasing the dose from 20 to 40 mg/day caused an additional incremental reduction but increasing it from 40 to 80 mg/day had no additional effect. This finding suggests that any clinical trial of lovastatin for the treatment or prevention of gallstones would best be carried out with a dose of 40 mg/day. Studies performed in a subset of four subjects revealed that time-course changes in the saturation index and low-density lipoprotein cholesterol were similar and reached plateaus by 1 week after 80 mg/day of lovastatin was either started or stopped.