BIOAVAILABILITY STUDY OF A NEW, SINKING, ENTERIC-COATED URSODEOXYCHOLIC ACID FORMULATION

A new enteric-coated ursodeoxycholic acid (UDCA) formulation which sin ks in the stomach and releases the drug only at a pH greater than or e qual to 6.5 was developed. In 12 healthy subjects we measured, using a specific enzyme immunoassay, the serum levels of UDCA after a single oral dose of 450 mg of UDCA in three different formulations; enteric c oated sinking tablet, stomach-floating enteric coated hard gelatin cap sule and conventional gelatin capsule. The drug was given after a meal . Results are expressed as mean+/-SD. The area under the curve [AUG, m u moll(-1) (8 h)] following oral administration of enteric-coated, sin king UDCA (39.0+/-8.5) was significantly higher than that obtained aft er both conventional UDCA (30.5+/-4.9) and floating enteric coated UDC A (29.3+/-3.4). Moreover, the maximum UDCA serum concentration (C-max) was significantly higher with the enteric coated sinking UDCA formula tion when compared to the other two formulations, while the time of ma ximum UDCA serum concentration (t(max)) occurred later. These results may be explained by the hypothesis that the sinking tablet is expelled in the latter phase of gastric emptying along with the solid content. It therefore reaches the intestine at the highest alkalization phase caused by sustained biliary and pancreatic secretions. When released, the protonated insoluble UDCA is promptly solubilized by the alkaline pH thus giving a higher UDCA concentration gradient which facilitates its passive absorption. On the other hand, the floating capsule reache s the intestine too early, still in presence of an acidic pH; and in t his condition UDCA is almost insoluble and consequently may be malabso rbed. The new formulation of UDCA seems to be an improvement with resp ect to commercially available UDCA formulations, where UDCA is only pa rtially absorbed (30-40% of the administered dose). The increased seru m AUC indicates an increased UDCA intestinal absorption and bioavailab ility that should lead to better accumulation of the drug in the enter ohepatic circulation and a more effective displacement of endogenous b ile acids.