Effect of clofibrate on the metabolism of bilirubin, bromosulphophthalein and indocyanine green and on the biliary lipid composition in Gilbert's syndrome.

Clofibrate (20 mg day-1 kg-1 body weight) given orally for 2 weeks to 18 subjects with Gilbert's syndrome reduced the total serum bilirubin concentration from 44.4 (22.1-71.7) mumol/l (median, range) to 15.0 (7.9-28.9) mumol/l, mainly by decreasing the 'indirect' fraction to 34.5% of pretreatment values. In contrast to treatment with phenobarbitone, clofibrate did not change the ratio of bilirubin mono- to di-conjugates in bile. The initial plasma disappearance rate of indocyanine green and of bromosulphophthalein did not show consistent changes during clofibrate treatment but the 'apparent' maximal biliary secretion capacity of bromosulphophthalein (Tm) decreased in most of the patients studied, whereas the relative storage capacity (S) tended to increase. As expected, the cholesterol saturation of bile increased in all subjects. These results suggest that clofibrate increases mainly the glucuronidation of bilirubin, promoting as such the overall hepatic transport in Gilbert's syndrome. However, it decreases the maximal biliary secretion of bromosulphophthalein, possibly by an increased hepatic retention. These phenomena might be linked to the augmented content of Z protein in the liver.