Pharmacokinetics and bioavailability of four modified-release ursodeoxycholic acid preparations for once-a-day administration.

Ursodeoxycholic acid (UDCA) is currently used for the treatment of cholestatic liver disease and for cholesterol gallstone dissolution. Various formulations have been designed to enhance its intestinal absorption or to improve patient compliance through once-a-day administration. The pharmacokinetics and bioavailability of four commercially available modified-release UDCA formulations (450 mg) were studied in 12 healthy subjects randomly receiving the four drugs under study. Serum samples were collected hourly for a 12-h period after administration and UDCA concentrations were measured using a specific enzyme immunoassay. For each formulation, Cmax, tmax, and the area under the curve (AUC) were determined and compared. Although all formulations were designed to provide sustained release, we observed different pharmacokinetics among the studied formulations. One of the formulations (sustained-release ursodeoxycholic acid Ratiopharm 450 mg tablets) showed high bioavailability, but failed to produce sustained release. In contrast, two other formulations (modified-release ursodeoxycholic acid Dorom 450 mg capsules and controlled-release Ursobil HT 450 mg capsules) provided sustained release, but did not offer efficient bioavailability. A fourth formulation (Ursilon retard 450 mg) exhibited gradual UDCA release lasting over 10 h, with efficient bioavailability, similar to that of conventional prompt-release formulations administered at the same dose. These data highlight the variability of commercially available sustained-release formulations. Manufacturers should be encouraged to provide drug kinetics and bioavailability data to further support the claimed pharmacokinetics.