title: Effects of a salt of cholestyramine and 2-[4-(p-chlorobenzoyl)phenoxy]2-methyl propionic acid (alpha-1081) on biliary lipid secretion in rats.
abstract: 1 Hypolipidaemic agents may increase biliary cholesterol in man, inducing a supersaturated bile. 2 To evaluate this possible side-effect, we have studied bile lipid secretion over a period of 8 h with intact enterohepatic circulation and 4 h with complete interruption in rats treated for two months with a salt of cholestyramine and 2-[4-(p-chlorobenzoyl)-phenoxy]2-methyl propionic acid (alpha-1081, 1.150 g/kg body wt., daily), cholestyramine (1.125 g/kg body wt. daily), procetofenic acid (25 mg/kg body wt. daily) and saline respectively (six rats for each group). 3 Cholesterol saturation index significantly (P less than 0.005) increased (from 0.21 +/- 0.01 to 0.39 +/- 0.09, mean +/- s.d.), in rats fed with procetofenic acid but it did not in alpha-1081- and cholestyramine-treated animals. 4 Procetofenic acid and, to a lesser extent, cholestyramine increased the bile flow. Procetofenic acid increased cholesterol secretion from 0.45 +/- 0.17 to 0.94 +/- 0.19 mumol kg-1 body wt. h-1 (mean +/- s.d.). 5 Cholestyramine increased both serum cholesterol and bile acid secretion from 0.45 +/- 0.17 to 0.68 +/- 0.10 and 25.8 +/- 9.48 to 39.96 +/- 6.68 mumol kg-1 body wt. h-1 respectively; alpha-1081, on the contrary, had no effect on bile lipid secretion. 6 These data suggest that alpha-1081 may be used as a new hypolipidaemic drug without any risk of increasing cholesterol in bile.
mesh_terms: D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism; D002782:Cholestenes / Q000009:adverse effects*; D002784:Cholesterol / Q000378:metabolism; D004338:Drug Combinations / Q000009:adverse effects; D011345:Fenofibrate / Q000009:adverse effects* / Q000031:analogs & derivatives; D000960:Hypolipidemic Agents / Q000009:adverse effects*; D050356:Lipid Metabolism; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D011422:Propionates / Q000009:adverse effects*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D001647:Bile Acids and Salts; D002782:Cholestenes; D004338:Drug Combinations; D000960:Hypolipidemic Agents; D010743:Phospholipids; D011422:Propionates; C014892:procetofenic acid; D002784:Cholesterol; D011345:Fenofibrate