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

ABSTRACT

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Ethyl propionate and isopropyl acetate are less toxic to the intestinal mucosa than MTBE, and ethyl propionate is more effective for gallstone dissolution.