ETHYL PROPIONATE IS MORE EFFECTIVE AND LESS CYTOTOXIC THAN METHYL TERT-BUTYL ETHER FOR TOPICAL GALLSTONE DISSOLUTION

Background & Aims: Ethyl propionate and isopropyl acetate were identif ied as gallstone solvents with more favorable physicochemical properti es than the currently used solvent methyl tert-butyl ether (MTBE). In this study, their efficacy and toxicity were compared. Methods: To com pare efficacy, matched stones from 33 patients were subjected to disso lution with each solvent. To evaluate cytotoxicity, jejunal segments o f the anesthetized rat were exposed to each solvent or saline; the seg ments were then perfused with markers for active absorption and passiv e permeability. Results: For 23 gallstone sets that dissolved complete ly with all three solvents, the average dissolution time was shorter w ith ethyl propionate (38 +/- 8 minutes) than with MTBE (60 +/- 13 minu tes) (P = 0.03) or isopropyl acetate (55 +/- 12 minutes) (P < 0.001). Four stones did not dissolve with ethyl propionate, seven with MTBE, a nd eight with isopropyl acetate. After 2 minutes of exposure to the so lvents, the dry weight of the segments decreased by 36% after MTBE but was unchanged after the other two solvents (P < 0.001), MTBE caused m ore 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 intesti nal mucosa than MTBE, and ethyl propionate is more effective for galls tone dissolution.