Ethyl propionate is more effective and less cytotoxic than methyl tert-butyl ether for topical gallstone dissolution.

Ethyl propionate and isopropyl acetate were identified as gallstone solvents with more favorable physicochemical properties than the currently used solvent methyl tert-butyl ether (MTBE). In this study, their efficacy and toxicity were compared. To compare efficacy, matched stones from 33 patients were subjected to dissolution with each solvent. To evaluate cytotoxicity, jejunal segments of the anesthetized rat were exposed to each solvent or saline; the segments were then perfused with markers for active absorption and passive permeability. For 23 gallstone sets that dissolved completely with all three solvents, the average dissolution time was shorter with ethyl propionate (38 +/- 8 minutes) than with MTBE (60 +/- 13 minutes) (P = 0.03) or isopropyl acetate (55 +/- 12 minutes) (P < 0.001). Four stones did not dissolve with ethyl propionate, seven with MTBE, and eight with isopropyl acetate. After 2 minutes of exposure to the solvents, the dry weight of the segments decreased by 36% after MTBE but was unchanged after the other two solvents (P < 0.001). MTBE caused more inhibition of active absorption than the other solvents (P < 0.001) and a greater increase in passive permeation (P < 0.03). Ethyl propionate and isopropyl acetate are less toxic to the intestinal mucosa than MTBE, and ethyl propionate is more effective for gallstone dissolution.