Ursodeoxycholic acid (ursodiol, ursodesoxycholic acid, Urso®, Ursolvan®) is a naturally occurring hydrophilic bile acid that is present in small amounts in human bile. It was first synthesised in Japan in the 1950s for its cholesterol antagonising properties, and has since been used in the treatment of cholesterol gallstone disease. It is marketed in Japan as Urso® by Tokyo Tanabe, a major supplier of ursodeoxycholic acid to Axcan. Ursodeoxycholic acid (Urso®) has had an orphan drug status in the US, where Axcan Pharma has launched it for the treatment of primary biliary cirrhosis. Axcan Schwarz has exclusive marketing rights for Urso® for the treatment of primary biliary cirrhosis for 7 years from the end of 1997. A phase II trial is underway in North America for the treatment of hypercholesterolaemia.Ursodeoxycholic acid is already launched in Canada for primary biliary cirrhosis, and is also launched in Canada and the US (as Actigall®; Novartis) for the dissolution of gallstones. It was marketed as Ursofalk® in Canada by Jouveinal, but this licensing agreement has been terminated since Jouveinal was acquired by Parke-Davis, and the drug is now marketed by Axcan Pharma as Urso®. Ursodeoxycholic acid is also launched in Spain as Ursochol® (Zambon), Ursobilane® (Estedi) and Ursolite® (Vita) for the dissolution of gallstones.Ursodeoxycholic acid is also undergoing phase II clinical trials at the Mayo Clinic, US for the prevention of colorectal cancer and the treatment of hepatitis C. The phase II trial for hepatitis C evaluated Urso® in combination with interferon-&agr;. Ursodeoxycholic acid is in a multicentre phase II trial for non-alcoholic steatohepatitis, and for primary sclerosing cholangitis.Ursodeoxycholic acid has demonstrated immunomodulatory properties, and the ability of Sanofi-Synthélabo's Ursolvan® to prevent acute liver transplant rejection has been tested in clinical trials in France.Axcan has renewed two agreements with Sanofi-Synthélabo for use, manufacture and sale of Urso® because of the expiration in the year 2000 of a previous 10-year agreement. The new licence for the US is valid until the expiration of the patents, in 2008, whereas for Canada, Axcan has acquired all rights on the patent pertaining to primary biliary cirrhosis.Alfa Farmaceutici is developing soluble formulations of ursodeoxycholic acid for the treatment of hepatic diseases and gallstones. The formulations allow targeted delivery of the drug into the first portion of the GI tract where absorption is optimal. Alfa's product is undergoing preclinical development in Italy.