In vitro dissolution of cholesterol gallstones. A study of factors influencing rate and a comparison of solvents.
Models of the common bile duct and gallbladder were constructed to study conditions that affect the rate of cholesterol gallstone dissolution by monooctanoin and other potential solvents. In the bile duct model, the rate of monooctanoin infusion was not an important factor in accelerating dissolution time. In contrast, the exclusion of bile from interfering with solvent-stone contact or the enhancement of solvent-stone contact by stirring significantly accelerated stone dissolution. The combination of both bile exclusion and stirring increased the dissolution rate of gallstones by monooctanoin 15-fold. When compared with two other ethers and with monooctanoin, methyl tert-butyl ether was found to be the most potent gallstone solvent. Methyl tert-butyl ether completely dissolved 219-mg cholesterol stones within 60 min. In the gallbladder model, in the absence of stirring both methyl tert-butyl ether and monooctanoin floated on bile, whereas the gallstones sank resulting in minimal stone-solvent contact. To increase the stone-solvent contact, we used a pump to create sufficient turbulence to mix the solvent with bile. Pump stirring of monooctanoin in the presence of bile achieved rates of stone dissolution approaching that of stirred monooctanoin without bile. Stirring of methyl tert-butyl ether and bile, however, did not achieve sufficient solvent-stone contact to appreciably accelerate dissolution in the presence of 50% bile. Stone-solvent contact was a critical factor in determining the rate of gallstone dissolution in both gallbladder and common bile duct models. Efforts to enhance contact include bile exclusion and intraluminal stirring--both of which are clinically applicable. Methyl tert-butyl ether is a potent new cholesterol gallstone solvent with excellent potential for use in humans. Even with this potent agent, however, rapid gallstone dissolution is likely to require removal of most of the bile from the dissolution medium.
D001646:Bile / Q000378:metabolism; D001652:Bile Ducts; D002210:Caprylates; D002769:Cholelithiasis / Q000188:drug therapy* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D004987:Ethers / Q000008:administration & dosage / Q000627:therapeutic use; D005704:Gallbladder; D005989:Glycerides / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D008738:Methyl Ethers; D008954:Models, Biological; D010477:Perfusion; D011677:Punctures; D012997:Solvents / Q000008:administration & dosage* / Q000627:therapeutic use; D013997:Time Factors
D002210:Caprylates; D004987:Ethers; D005989:Glycerides; D008738:Methyl Ethers; D012997:Solvents; C043243:methyl tert-butyl ether; D002784:Cholesterol; C025343:monooctanoin