Kinetics of cholesterol gallstone dissolution by glycocheno-, glyco-ursodeoxycholic acid, and mixtures of both in vitro.
Cheno- and ursodeoxycholic acid feeding are both efficient in conservative gallstone therapy. Urso decreases biliary cholesterol excretion even more than cheno. Glyco-urso becomes dose dependent the predominant bile acid conjugate in bile under urso feeding. We therefore studied the kinetics of cholesterol gallstone dissolution in aqueous solutions of 100 mM glyco-cheno, 100 mM glyco-urso, and mixtures of both consisting of 40 mM glyco-urso plus 60 mM glyco-cheno and 80 mM glyco-urso plus 20 mM glyco-cheno in vitro. The daily dissolution rates of cholesterol achieved by these solutions were for 100 mM glyco-cheno 0.87 +/- 0.1 mg (mean +/- SEM), for 40 mM glyco-urso plus 60 mM glyco-cheno 0.28 +/- 0.003 mg, for 80 mM glyco-urso plus 20 mM glyco-cheno 0.07 +/- 0.002 mg, and for 100 mM glyco-urso 0.07 +/- 0.03 mg. Correspondingly were the weight decreases of the gallstones by 100 mM glyco-cheno 1.2 +/- 0.1 mg/day, by 40 mM glyco-urso plus 60 mM glyco-cheno 0.3 +/- 0.01 mg/day, by 80 mM glyco-urso plus 20 mM glyco-cheno 0.11 +/- 0.02 mg/day, and by 100 mM glyco-urso 0.1 +/- 0.02 mg/day. Complete gallstone dissolution occurred during the observation time of 4 months only by 100 mM glyco-cheno in 12.8 +/- 3.3 weeks. Thus glyco-urso dissolves only little cholesterol and decreases the speed of cholesterol gallstone dissolution. It is concluded that high doses of urso in gallstone therapy which lead to great amounts of glyco-urso in bile may diminish gallstone dissolution rates.
D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives*; D002769:Cholelithiasis / Q000188:drug therapy* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003840:Deoxycholic Acid / Q000031:analogs & derivatives*; D004347:Drug Interactions; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005999:Glycochenodeoxycholic Acid / Q000627:therapeutic use*; D006801:Humans; D007700:Kinetics; D014580:Ursodeoxycholic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D005999:Glycochenodeoxycholic Acid; C024033:glycoursodeoxycholic acid; D014580:Ursodeoxycholic Acid; D002784:Cholesterol; D005998:Glycine