Dear All,

Could some one please suggest procedure and statistical plan for proving Bioequivalence in healthy human subjects of the molecule which is present endogenously also (Ursodeoxycholic acid). Which moiety to be considered for BE.

Of the two bioanalytes (Ursodiol & Glycine dioxycholic acid), which is free and which is conjugated. If any references are available kindly forward the same.

Thanx in advance

Ursodeoxycholic acid is a secondary bile acid formed in the intestine. It involved in the emulsification of fats in intestine. it is choleretic and decreases the concentration of cholesterol in the bile. The pharmaceutical preparation, called ursodiol, is used to treat biliary diseases by dissolving radiolucent and noncalcifying gallstones. Ursodiol is a white powder with a bitter taste; insoluble in water, slightly soluble in chloroform, in ether; soluble in ethanol and glacial acetic acid; melting point 203 - 204 C; administered orally. The chemical name is 3a,7b-dihydroxy-5b-cholan-24-oic acid.

Bile is a bitter, yellow to greenish fluid composed of glycine or taurine conjugated bile salts, cholesterol, phospholipid, bilirubin diglucuronide, and electrolytes. It is secreted by the liver and delivered to the duodenum to aid the process of digestion and fat absorption by emulsification of fat products in the upper small intestine. They play role dissolving cholesterol and accretes into lumps in the gall bladder, forming gallstones. Bile's bicarbonate constituents serves for alkalinizing the intestinal contents. Bile is responsible for as the route of excretion for hemoglobin breakdown products (bilirubin). Excretion of bile salts by liver cells and secretion of bicarbonate rich fluid by ductular cells in response to secretin are the major factors which normally determine the volume of secretion. Bile acids are liver-generated steroid carboxylic acids. The primary bile acids (cholic and chenodeoxycholic acid) are conjugated with either glycine or taurine in the form of taurocholic acid and glycocholic acid. The secondary bile acids (deoxycholic, lithocholic, and ursodeoxycholic acid) are formed from the primary bile acids by the action of intestinal bacteria. They are soluble in alcohol and acetic acid. The lithocolyl conjugates are relatively insoluble; excreted mostly in the form of sulfate esters like sulfolithocholylglycine. Most of the bile acids are reabsorbed and returned to the liver via enterohepatic circulation, where, after free acids are reconjugated, they are again excreted.

Cholic Acid
Methyl Cholate
Deoxycholic Acid
Dehydrocholic Acid
Methyl Deoxycholate
Chenodeoxycholic Acid
Methyl Chenodeoxycholate
Sodium Glycocholate
Glycodeoxycholic Acid
Sodium Glycodeoxycholate
Sodium Taurocholate
Sodium Taurodeoxycholate
Ursodeoxycholic acid