We performed experiments in anesthetized piglets with two
cholesterol gallstone solvents,
methyl tert-butyl ether and
ethyl propionate, to determine 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; intraluminal 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 piglets 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 gradually; plasma levels decreased by half in 90 min. In contrast, when
ethyl propionate was infused for 2 or 6 hr, blood levels remained below the detection limit, probably because of high first-pass hepatic extraction. We conclude that, under conditions simulating those likely present in patients undergoing contact dissolution of gallbladder stones, the two
solvents differ:
Ethyl propionate is removed so rapidly from blood that its levels remain undetectable, whereas
methyl tert-butyl ether levels in blood (and, presumably, peripheral tissues) increase continuously.(ABSTRACT TRUNCATED AT 250 WORDS)