TY - JOUR T1 - THE EFFECT OF OBSTRUCTIVE JAUNDICE ON DRUG METABOLISM IN RABBITS JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 7 LP - 11 VL - 131 IS - 1 AU - Edwin F. McLuen AU - James R. Fouts Y1 - 1961/01/01 UR - http://jpet.aspetjournals.org/content/131/1/7.abstract N2 - Obstructive jaundice affects liver microsomal drug metabolism in rough proportion to the degree of histologically observable cell damage. Livers with mild cellular damage often retain essentially normal hexobarbital metabolism while other pathways are markedly reduced from normal levels. Severe cellular damage leads to nearly complete loss of all the drug enzyme activities studied. In vitro, sodium deoxycholate inhibits most drug enzyme activities at about the same final concentration—50% inhibition at approximately 1 x 10-2 M. The curves of enzyme inhibition and those of microsomal solubilization (Palade and Siekevitz, 1956) by deoxycholate can almost be superimposed on one another. This suggests that the two phenomena may be related. Deoxycholate effects on drug metabolism cannot be reversed by dialysis of the enzyme-bile acid mixture against distilled water. This too would be consistent with an inhibition-by-destruction mechanism. The prolongation of sleeping times seen when jaundiced and normal rabbits are compared is compatible with the effects of deoxycholate on the drug enzyme systems in vitro. ER -