A Combination of Chenodeoxycholic Acid and Ursodeoxycholic Acid is more Effective than Either Alone in Reducing Biliary Cholesterol Saturation^†

The effects on biliary lipids of 10 mg per kg per day of chenodeoxycholic acid (CDCA), 10 mg per kg per day of ursodeoxycholic acid (UDCA), and their equimolar combination (5 mg per kg per day of each), all administered for 45 to 60 days, were investigated in 18 patients with gallstones in a double-blind study with a balanced latin square design. The molar percentage of cholesterol in bile (initial value 9.7 ± 2.2) was significantly lower after UDCA (5.4 ± 1.3) and the combination (5.2 ± 1.2) than after CDCA (7.2 ± 1.7).

Nevertheless, when the ability to solubilize cholesterol was calculated, taking into account the percentage of biliary UDCA, then the differences in cholesterol saturation induced by UDCA alone and the combination also became considerable (saturation index: 0.94 ± 0.12 as compared to 0.81 ± 0.12).

The total bile acid pool increased significantly after treatment with CDCA and the combination, but not after UDCA. Lithocholic acid was increased significantly only by treatment with CDCA.

Diarrhea was observed in five patients with hypertransaminasemia and in four patients after CDCA, whereas both UDCA and the combination were well-tolerated.

We conclude that the administration of a combination of equimolar doses of CDCA and UDCA can be recommended for medical treatment of gallstones since it has greater effects on bile cholesterol saturation than either alone, is better tolerated than CDCA, and is less expensive than UDCA.