title: Addition of dimethylsulphoxide to methyl-tert-butyl ether and ethyl propionate increases cholesterol dissolving capacity and cholesterol gall stone dissolution in vitro.
abstract: There is a discrepancy between in vitro cholesterol dissolving efficacy of methyl-tert-butyl ether (MTBE) and ethyl propionate and cholesterol gall stone dissolution in vivo. This study investigated whether the presence of bile changes the cholesterol dissolving capacity of MTBE and ethyl propionate. The addition of dimethylsulphoxide to MTBE or ethyl propionate was also studied to discover if it improves the dissolving capacity for cholesterol gall stones. The presence of bile caused a 25% decrease in cholesterol dissolving capacity of both MTBE and ethyl propionate (p < 0.0001). This inhibitory effect of bile could be overcome by the addition of dimethyl-sulphoxide: dimethylsulphoxide caused an increase in cholesterol dissolving capacity of MTBE and ethyl propionate, the increase depending on the dimethyl-sulphoxide/bile ratio in the mixture. Mean dissolution time of weight, size, and patient matched cholesterol gall stones was 220 minutes in MTBE and 130 minutes in MTBE/dimethylsulphoxide (p < 0.0001). No stones dissolved completely in ethyl propionate or ethyl propionate/dimethyl-sulphoxide within 300 minutes. In conclusion, MTBE/dimethylsulphoxide is a more potent dissolving agent for cholesterol gall stones than MTBE, giving a 40% reduction in dissolution time. Addition of dimethylsulphoxide to ethyl propionate does not result in faster stone dissolution. MTBE and MTBE/dimethylsulphoxide are far superior to ethyl propionate as solvents for cholesterol gall stones.
authors: Department of Gastroenterology, University of Amsterdam, The Netherlands.
authors: J J
authors: JJ
authors: Bergman
authors: A K
authors: AK
authors: Groen
authors: K
authors: K
authors: Huibregtse
authors: G N
authors: GN
authors: Tytgat
mesh_terms: D001646:Bile; D002769:Cholelithiasis / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004338:Drug Combinations; D004987:Ethers / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008738:Methyl Ethers; D011422:Propionates / Q000494:pharmacology*; D012995:Solubility / Q000187:drug effects; D012997:Solvents / Q000494:pharmacology*; D013997:Time Factors; D014867:Water / Q000494:pharmacology
chemical_list: D004338:Drug Combinations; D004987:Ethers; D008738:Methyl Ethers; D011422:Propionates; D012997:Solvents; D014867:Water; C043243:methyl tert-butyl ether; D002784:Cholesterol; C069373:ethyl propionate; D004121:Dimethyl Sulfoxide