Zakko S F, Scirica J C, Guttermuth M C, Dodge J, Hajjar J J
Department of Medicine, University of Connecticut School of Medicine, Farmington 06030, USA.
Gastroenterology. 1997 Jul;113(1):232-7. doi: 10.1016/s0016-5085(97)70100-8.
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.
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.
丙酸乙酯和乙酸异丙酯被鉴定为胆石溶解剂,其理化性质比目前使用的溶剂甲基叔丁基醚(MTBE)更具优势。在本研究中,对它们的疗效和毒性进行了比较。
为比较疗效,将33例患者匹配的结石分别用每种溶剂进行溶解。为评估细胞毒性,将麻醉大鼠的空肠段暴露于每种溶剂或盐水中;然后用活性吸收和被动通透性标记物对这些肠段进行灌注。
对于23组能被所有三种溶剂完全溶解的胆结石,丙酸乙酯的平均溶解时间(38±8分钟)比MTBE(60±13分钟)短(P = 0.03),比乙酸异丙酯(55±12分钟)短(P < 0.001)。有4颗结石不能被丙酸乙酯溶解,7颗不能被MTBE溶解,8颗不能被乙酸异丙酯溶解。暴露于溶剂两分钟后,MTBE处理后的肠段干重下降了36%,而其他两种溶剂处理后的肠段干重未发生变化(P < 0.001)。MTBE比其他溶剂对活性吸收的抑制作用更强(P < 0.001),对被动通透性的增加作用更大(P < 0.03)。
丙酸乙酯和乙酸异丙酯对肠黏膜的毒性比MTBE小,且丙酸乙酯在胆石溶解方面更有效。