Gallstone dissolution with bile acids

Reduction of ketones. Reduction of ketones with metals in an alcohol is one of the earliest methods for effecting reduction of ketones, and is still useful since it can proceed with stereoselectivity opposite to that obtained with metal hydrides.1 An example is the reduction of the 3a-hydroxy-7-ketocholanic acid 1 to the diols 2 and 3. The former, ursodesoxycholic acid, a rare bile acid found in bear bile, is used in medicine for dissolution of gallstones. The stereochemistry is strongly dependent on the nature of the reducing agent (equation I).2 Sodium dithionite and sodium borohydride reductions result mainly in the 7a-alcohol, whereas reductions with sodium or potassium in an alcohol favor reduction to the 7p-alcohol. More recently3 reduction of 1 to 2 and 3 in the ratio 96 4 has been achieved with K, Rb, and Cs in f-amyl alcohol. Almost the same stereoselectivity can be obtained by addition of potassium, rubidium, or cesium salts to reductions of sodium in t-amyl alcohol. This cation effect has not been observed previously. 

Chenodiol, a bile acid with cholehtholytic properties (250 mg b.i.d. for 2 weeks), is indicated in dissolution of radiolucent cholesterol stones (gallstones) when systemic disease or age... 

Ursodiol (ursodeoxycholic acid—UDCA), a bile acid with gallstone-stabilizing properties (8 to 10 mg/kg/day), is used for dissolution of radiolucent gallbladder stones and to increase the flow of bile in patients with bile duct prosthesis or stents. 

Rowachol has been in use for over 50 years for the dissolution of gallstones and biliary tract stones. There have been many published works as to its effects and at least one double-blind trial (Lamy, 1967). It has been stated that although the dissolution rate of Rowachol is not impressive, it is still much greater than could occur spontaneously (Doran and Bell, 1979). It has been employed alone as a useful therapy for common duct stones (Ellis and Bell, 1981), although improved results were demonstrated when Rowachol was used in conjunction with bile acid therapy (Ellis et al., 1981). 

Ellis, W. R., Bell, G. D., Middleton, B., White, D. A. 1981. An adjunct to bile acid therapy for gallstone dissolution—Combination of low dose chenodeoxycholic acid with a terpene preparation. Br. Med. J. 1 611-612. 

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