INCREASED BLOOD-LEVELS OF METHYL TERT-BUTYL ETHER BUT NOT OF ETHYL PROPIONATE DURING INSTILLATION WITH CONTACT GALLSTONE DISSOLUTION AGENTSIN THE PIG

We performed experiments in anesthetized piglets with two cholesterol gallstone solvents, methyl tert-butyl ether and ethyl propionate, to d etermine whether blood levels of either solvent would increase during gallbladder instillation of these solvents under conditions simulating gallstone dissolution. The solvent was oscillated rapidly in and out of the gallbladder with a computer-controlled syringe pump; intralumin al pressure was set below the leakage pressure, and oscillating volume was set below the leakage volume to decrease loss of solvent into the intestine. Blood levels were measured with gas chromatography. Six pi glets received methyl tert-butyl ether, and six piglets received ethyl propionate. During 2 hr of instillation with methyl tert-butyl ether, blood levels increased steadily to concentrations averaging 0.3 ml/L blood at 2 hr; during a 6-hr period of instillation. blood levels rose to above 0.4 ml/L blood. Replacement of methyl tert-butyl ether with saline solution in the gallbladder caused blood levels to decline grad ually, plasma levels decreased by half in 90 min. In contrast, when et hyl propionate was infused for 2 or 6 hr, blood levels remained below the detection limit, probably because of high first-pass hepatic extra ction. We conclude that, under conditions simulating those likely pres ent in patients undergoing contact dissolution of gallbladder stones, the two solvents differ: Ethyl propionate is removed so rapidly from b lood that its levels remain undetectable, whereas methyl tert-butyl et her levels in blood (and, presumably, peripheral tissues) increase con tinuously. If the absorption from the gallbladder and subsequent metab olism of ethyl propionate and methyl tert-butyl ether in human beings are similar to those of the piglet, side effects attributable to incre ased blood levels will be fewer if ethyl propionate is used than if me thyl tert-butyl ether is used for contact dissolution of cholesterol g allstones.